High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma.

PubMed

Abdel-Fatah, Tarek M A; Powe, Desmond G; Hodi, Zsolt; Lee, Andrew H S; Reis-Filho, Jorge S; Ellis, Ian O

2007-03-01

This study was undertaken to determine the morphologic features and frequency of putative precursor lesions involved in the development of some pure forms of special types and low grade breast carcinoma. We reviewed 147 successive tumor cases, comprising tubular carcinoma (TC); pure type (n=56) and mixed type (n=20), invasive lobular carcinoma (ILC); classic type (n=57), and tubulolobular carcinoma (TLC; n=14). The presence of preinvasive lesions including columnar cell lesions (CCLs), usual epithelial hyperplasia, ductal carcinoma in situ (DCIS), and lobular neoplasia (LN) was determined. Estrogen receptor and E-cadherin immunohistochemistry was performed. Ninety-five percent (95%) of pure TCs had associated CCLs with the majority showing flat epithelial atypia. Atypical ductal hyperplasia (ADH)/DCIS was present in 89% patients. Colocalization of CCL, ADH/DCIS, and TC was seen in 85% patients, all displaying the same cytologic-nuclear morphology in most cases. LN was seen in 16%. In ILC, 91% cases showed LN. CCL and ADH/DCIS were seen in 60% and 42% cases, respectively. E-cadherin was positive in TLC but reduced in TC and completely absent in ILC. In conclusion, our findings support the hypothesis that CCLs are associated with pure and mixed forms of TC, and that LN is involved in ILC development. Our observations suggest that these lesions represent family members of low grade precursor, in situ and invasive neoplastic lesions of the breast. Molecular studies are being performed to substantiate the hypothesis that tubular and lobular carcinomas have direct evolutionary links to CCLs and flat epithelial atypia.

Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy.

PubMed

Graesslin, O; Antoine, M; Chopier, J; Seror, J Y; Flahault, A; Callard, P; Daraï, E; Uzan, S

2010-02-01

Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery. From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought. VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB (p=0.04 versus ALH). ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast

PubMed Central

2014-01-01

Background This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. Methods A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. Results Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa = 0.38), columnar cell hyperplasia (CCH; Kappa = 0.32), while a moderate agreement (Kappa = 0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa = 0.62) and lobular carcinoma in situ (LCIS; Kappa = 0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa = 0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa = 0.44), low-grade DCIS (Kappa = 0.47), intermediate-grade DCIS (Kappa = 0.45), and DCIS with microinvasion (Kappa = 0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa = 0.68). Conclusions According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725. PMID:24948027

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast.

PubMed

Gomes, Douglas S; Porto, Simone S; Balabram, Débora; Gobbi, Helenice

2014-06-19

This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa=0.38), columnar cell hyperplasia (CCH; Kappa=0.32), while a moderate agreement (Kappa=0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa=0.62) and lobular carcinoma in situ (LCIS; Kappa=0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa=0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa=0.44), low-grade DCIS (Kappa=0.47), intermediate-grade DCIS (Kappa=0.45), and DCIS with microinvasion (Kappa=0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa=0.68). According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725.

EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.

PubMed

Wang, Chao-Qun; Li, Yang; Huang, Bi-Fei; Zhao, Yong-Ming; Yuan, Hui; Guo, Dongfang; Su, Chen-Ming; Hu, Gui-Nv; Wang, Qian; Long, Tengyun; Wang, Yan; Tang, Chih-Hsin; Li, Xiaoni

2017-11-15

Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.

Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

PubMed Central

Ulich, T. R.; Yi, E. S.; Cardiff, R.; Yin, S.; Bikhazi, N.; Biltz, R.; Morris, C. F.; Pierce, G. F.

1994-01-01

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male rats. KGF causes proliferation of ductal and acinar cells in the mammary glands of pregnant rats. On the other hand, the ductal epithelium of lactating postpartum rats is resistant to the proliferative action of KGF. The mammary glands of lactating rats did not express less KGF receptor mRNA than the glands of pregnant rats, suggesting that the resistance of the ductal epithelium to KGF during lactation is not related to KGF receptor mRNA down-regulation. The mammary glands of both pregnant and postpartum lactating rats express KGF mRNA with more KGF present in the glands of lactating rats. In conclusion, the KGF and KGF receptor genes are expressed in rat mammary glands and recombinant KGF is a potent growth factor for mammary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178937

Stromal and Epithelial Caveolin-1 Both Confer a Protective Effect Against Mammary Hyperplasia and Tumorigenesis

PubMed Central

Williams, Terence M.; Sotgia, Federica; Lee, Hyangkyu; Hassan, Ghada; Di Vizio, Dolores; Bonuccelli, Gloria; Capozza, Franco; Mercier, Isabelle; Rui, Hallgeir; Pestell, Richard G.; Lisanti, Michael P.

2006-01-01

Here, we investigate the role of caveolin-1 (Cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. Cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of Cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. To address this issue, we characterized the development of the mammary ductal system in Cav-1−/− mice and performed a series of mammary transplant studies, using both wild-type and Cav-1−/− mammary fat pads. Cav-1−/− mammary epithelia were hyperproliferative in vivo, with dramatic increases in terminal end bud area and mammary ductal thickness as well as increases in bromodeoxyuridine incorporation, extracellular signal-regulated kinase-1/2 hyperactivation, and up-regulation of STAT5a and cyclin D1. Consistent with these findings, loss of Cav-1 dramatically exacerbated mammary lobulo-alveolar hyperplasia in cyclin D1 Tg mice, whereas overexpression of Cav-1 caused reversion of this phenotype. Most importantly, Cav-1−/− mammary stromal cells (fat pads) promoted the growth of both normal mammary ductal epithelia and mammary tumor cells. Thus, Cav-1 expression in both epithelial and stromal cells provides a protective effect against mammary hyperplasia as well as mammary tumorigenesis. PMID:17071600

Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3

PubMed Central

Turner-Ivey, Brittany; Smith, Ericka L.; Rutkovsky, Alex C.; Spruill, Laura S.; Mills, Jamie N.

2018-01-01

Purpose NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo. Methods We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin. Results Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50 weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ. Conclusions Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene. PMID:28484924

Immediate surgical resection of residual microcalcifications after a diagnosis of pure flat epithelial atypia on core biopsy: a word of caution.

PubMed

Noël, Jean-Christophe; Buxant, Frédéric; Engohan-Aloghe, Corinne

2010-12-01

The entity of pure flat epithelial atypia remains a challenge due to controversy of the surgical management of residual microcalcifications after core needle biopsies. This study aims to assess the morphological data observed in immediate surgical resection specimen of residual microcalcifications after a diagnosis of pure flat epithelial atypia on mammotome core biopsy. Sixty-two mammotome core biopsy with a diagnosis of pure flat epithelial atypia (flat epithelial atypia without associated atypical ductal hyperplasia, in situ and/or invasive carcinoma) were identified. From these 62 cases, 20 presented residual microcalcifications and underwent an immediate surgical excision after mammotome. Of the 20 patients with excised microcalcifications, 8 (40%)cases had residual pure flat epithelial atypia, 4 (20%) cases had atypical ductal hyperplasia, 4 (20%) cases had lobular in situ neoplasia, no lesions were retrieved in 4 (20%) case. None of the patients had either in situ ductal carcinoma and/or invasive carcinoma. Surgical resection of residual microcalcifications after the diagnosis of pure flat epithelial atypia on core needle biopsy remains still a debate. The present study shows no cases of in situ ductal and/or invasive carcinoma on immediate excision of residual microcalcifications after mammotome core biopsies. Copyright © 2009 Elsevier Ltd. All rights reserved.

Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

PubMed

Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

2008-09-01

Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics.

PubMed

Weinfurtner, R Jared; Patel, Bhavika; Laronga, Christine; Lee, Marie C; Falcon, Shannon L; Mooney, Blaise P; Yue, Binglin; Drukteinis, Jennifer S

2015-06-01

Analysis of magnetic resonance imaging-guided breast biopsies yielding high-risk histopathologic features at a single institution found an overall upstage rate to malignancy of 14% at surgical excision. All upstaged lesions were associated with atypical ductal hyperplasia. Flat epithelial atypia and atypical lobular hyperplasia alone or with lobular carcinoma in situ were not associated with an upstage to malignancy. The purpose of the present study w as to determine the malignancy upstage rates and imaging features of high-risk histopathologic findings resulting from magnetic resonance imaging (MRI)-guided core needle breast biopsies. These features include atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and lobular carcinoma in situ (LCIS). A retrospective medical record review was performed on all MRI-guided core needle breast biopsies at a single institution from June 1, 2007 to December 1, 2013 to select biopsies yielding high-risk histopathologic findings. The patient demographics, MRI lesion characteristics, and histopathologic features at biopsy and surgical excision were analyzed. A total of 257 MRI-guided biopsies had been performed, and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant upstage rate to malignancy compared with the other high-risk histopathologic subtypes combined. No specific imaging characteristics on MRI were associated with an upstage to malignancy on the statistical analysis. MRI-guided breast biopsies yielding high-risk histopathologic features were associated with an overall upstage to malignancy rate of 14% at surgical excision. All upstaged lesions were associated with ADH. FEA and ALH alone or with LCIS were not associated with an upstage to malignancy. Copyright © 2015 Elsevier Inc. All rights reserved.

Feasibility and safety of placement of a newly designed, fully covered self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot study (with video).

PubMed

Park, Do Hyun; Kim, Myung-Hwan; Moon, Sung-Hoon; Lee, Sang Soo; Seo, Dong-Wan; Lee, Sung-Koo

2008-12-01

Painful chronic pancreatitis with main pancreatic ductal strictures is usually managed with endotherapy with a plastic stent. To date, the role of placement of metallic stents, especially uncovered ones in benign pancreatic ductal stricture, has been unsatisfactory as a result of stent dysfunction related to mucosal hyperplasia. We explored the feasibility and safety of temporary placement of a newly designed, fully covered self-expandable metal stent (FCSEMS) in painful chronic pancreatitis and refractory benign pancreatic ductal strictures. A prospective pilot and feasibility study. A tertiary academic center. Thirteen patients with chronic painful pancreatitis of alcoholic (8) or idiopathic (5) etiology. ERCP with temporary FCSEMS placement (2 months). Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. End points were feasibility, safety, and morbidity. Successful FCSEMS placement was performed in all enrolled patients. After immediate placement of FCSEMS, 2 patients had mild acute pancreatitis related mainly to the stricture dilation procedure (Soehendra stent retriever or balloon dilation). Complications associated with stent placement included 5 migrations (39%, 1 proximal and 4 distal) and 2 incidents of cholestatic liver dysfunction associated with the compression of the bile duct orifice by expansion of FCSEMSs. In 1 patient with proximal migration, the stent was repositioned by an inflated retrieval balloon. Additional endoscopic biliary sphincterotomy with or without biliary stenting was performed in 2 patients with cholestatic liver dysfunction. There was no occurrence of pancreatic sepsis among any patients. FCSEMSs were removed from 9 of 9 patients without stent migration (100% [9/9] as per protocol, and 69% [9/13] as intention to treat, respectively). Improvement or resolution of the pancreatic ductal strictures was confirmed in all 13 patients on follow-up ERCP (2 months after stent placement), regardless of stent migration. Small patient populations without long-term follow-up. Two-month placement of FCSEMSs in patients with refractory benign pancreatic ductal strictures may be feasible and relatively safe. However, stent migration was not uncommon. A further investigation with ideal stent design may therefore be needed before recommending FCSEMSs as a therapeutic option for refractory benign pancreatic ductal strictures.

A morphologic analysis of 'naked' islets of Langerhans in lobular atrophy of the pancreas.

PubMed

Suda, K; Tsukahara, M; Miyake, T; Hirai, S

1994-08-01

The 'naked' islets of Langerhans (NIL) in randomly selected autopsy cases and in cases of chronic alcoholic pancreatitis, cystic fibrosis, and pancreatic carcinoma were studied histopathologically. The NIL were found in 55 of 164 randomly selected cases, with age-related frequency, in 21 of 30 cases of chronic alcoholic pancreatitis, in 2 of 2 cases of cystic fibrosis, and in 25 of 32 cases of pancreatic carcinoma. The NIL were frequently accompanied by ductal alterations: epithelial metaplasia and hyperplasia in randomly selected cases, protein plugs in chronic alcoholic pancreatitis, mucus plugs in cystic fibrosis, and obliterated ducts in pancreatic carcinoma. The NIL in randomly selected cases may have been formed by ductal alterations that caused stenosis of the lumen, those in chronic alcoholic pancreatitis and cystic fibrosis were the result of protein or mucus plugging, and those in pancreatic carcinoma were a result of neoplastic involvement of the distal pancreatic duct. Therefore, the common factor in the development of NIL is thought to be obstruction of the pancreatic duct system, and in cases of NIL that have a multilobular distribution and interinsular fibrosis, a diagnosis of chronic pancreatitis can usually be made.

Flat epithelial atypia of the breast.

PubMed

Lerwill, Melinda F

2008-04-01

Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The atypical cells maintain a "flat" pattern of growth without evidence of architectural atypicality. Morphologic, immunohistochemical, and molecular investigations support that flat epithelial atypia represents an early step in the evolution of low-grade ductal carcinomas. It is frequently seen in association with atypical ductal hyperplasia, low-grade ductal carcinoma in situ, invasive tubular carcinoma, and lobular neoplasia. The risk for subsequent breast carcinoma remains to be defined, but flat epithelial atypia likely represents a nonobligate precursor with an extended time course to progression. Certain benign alterations may superficially mimic its appearance; careful attention to cytologic and architectural characteristics can help one distinguish these unrelated entities from flat epithelial atypia.

Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions

PubMed Central

2010-01-01

Background Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Methods Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues. Results Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs. Conclusion The remarkable similarity of feline mammary IELs to those of humans, with the tendency to lose hormone receptor expression in atypical IELs, supports the cat as a possible model to study ER- and PR-negative breast lesions. PMID:20412586

Columnar cell lesions on breast needle biopsies: is surgical excision necessary? A systematic review.

PubMed

Verschuur-Maes, Anoek H J; van Deurzen, Carolien H M; Monninkhof, Evelyn M; van Diest, Paul J

2012-02-01

This systematic review was conducted to provide treatment recommendations for patients with a diagnosis of columnar cell lesions (CCLs) in a breast core needle biopsy (CNB). CCLs are putative breast cancer precursors and are often associated with (in situ) carcinoma in excision specimens. Although several studies reported on the progression risk and underestimation rate of a CNB diagnosis of CCL, there is no consensus regarding optimal clinical management in this context. We searched MEDLINE, Embase, and Cochrane databases from 1990 to October 2010 for studies on patients with a CNB diagnosis of CCL without atypia, CCL with atypia and atypical ductal hyperplasia associated with CCL followed by surgical excision or clinical follow up. Of 1759 selected articles, 24 were included in this review. The pooled underestimation risks for (in situ) carcinoma were as follow: CCL without atypia 1.5% (95% confidence interval [CI] 0.6%-4%), CCL with atypia 9% (95% CI: 5%-14%), and atypical ductal hyperplasia associated with CCL 20% (95% CI: 13%-28%), based on the whole groups of patients with a CNB. Studies including CCLs with long-term clinical follow-up showed a trend toward a limited elevated breast cancer risk. On the basis of the (in situ) carcinoma underestimation rates of patients with a CNB diagnosis of CCL with atypia and atypical ductal hyperplasia associated with CCL, surgical excision should be considered. For CCL without atypia, more studies with a long-term follow-up are required, but so far, surgical excision biopsy does not seem to be necessary.

Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies.

PubMed

Calhoun, Benjamin C; Sobel, Amy; White, Richard L; Gromet, Matt; Flippo, Teresa; Sarantou, Terry; Livasy, Chad A

2015-05-01

Flat epithelial atypia of the breast commonly co-exists with atypical ductal hyperplasia, lobular neoplasia, and indolent forms of invasive carcinomas such as tubular carcinoma. Most patients with pure flat epithelial atypia on core biopsy undergo surgical excision to evaluate for carcinoma in the adjacent breast tissue. Studies to date have reported varying upgrade rates with most recommending follow-up excision. These studies have often lacked detailed radiographic correlation, central review by breast pathologists and information regarding the biology of the carcinomas identified upon excision. In this study, we report the frequency of upgrade to invasive carcinoma or ductal carcinoma in situ in excision specimens following a diagnosis of pure flat epithelial atypia on core biopsy. Radiographic correlation is performed for each case and grade/receptor status of detected carcinomas is reported. Seventy-three (73) core biopsies containing pure flat epithelial atypia were identified from our files, meeting inclusion criteria for the study. In the subsequent excision biopsies, five (7%) cases contained invasive carcinoma or ductal carcinoma in situ and seventeen (23%) contained atypical ductal hyperplasia or lobular neoplasia. All of the ductal carcinoma in situ cases with estrogen receptor results were estrogen receptor positive and intermediate grade. The invasive tumors were small (pT1a) hormone receptor-positive, HER2-negative, low-grade invasive ductal or tubular carcinomas with negative sentinel lymph-node biopsies. No upgrades were identified in the 14 patients who had all of their calcifications removed by the stereotactic core biopsy. Our rate of upgrade to carcinoma, once cases with discordant imaging are excluded, is at the lower end of the range reported in the literature. Given the low upgrade rate and indolent nature of the carcinomas associated with flat epithelial atypia, case management may be individualized based on clinical and radiographic findings. Excision may not be necessary for patients without remaining calcifications following core biopsy.

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases.

PubMed

Alsadoun, Nadjla; MacGrogan, Gaëtan; Truntzer, Caroline; Lacroix-Triki, Magali; Bedgedjian, Isabelle; Koeb, Marie-Hélène; El Alam, Elsy; Medioni, Dan; Parent, Michel; Wuithier, Pascal; Robert, Isabelle; Boidot, Romain; Arnould, Laurent

2018-05-21

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors.

Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

PubMed

Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

2009-09-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

Targeted Overexpression of EZH2 in the Mammary Gland Disrupts Ductal Morphogenesis and Causes Epithelial Hyperplasia

PubMed Central

Li, Xin; Gonzalez, Maria E.; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D.; Kleer, Celina G.

2009-01-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with β-catenin, inducing β-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/β-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with β-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma. PMID:19661437

Flat Epithelial Atypia of the Breast.

PubMed

Collins, Laura C

2009-06-01

Lesions of the breast characterized by enlarged terminal duct lobular units lined by columnar epithelial cells are being encountered increasingly in breast biopsy specimens. Some of these lesions feature cuboidal to columnar epithelial cells in which the lining cells exhibit cytologic atypia. The role of these lesions (recently designated "flat epithelial atypia" [FEA]) in breast tumor progression is still emerging. FEA commonly coexists with well-developed examples of atypical ductal hyperplasia, low-grade ductal carcinoma in situ, lobular neoplasia, and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. Additional studies are needed to better understand the biologic nature and clinical significance of these lesions. Copyright © 2009 Elsevier Inc. All rights reserved.

[Atypical epithelial hyperplasia of the breast: current state of knowledge and clinical practice].

PubMed

Lavoué, V; Bertel, C; Tas, P; Bendavid, C; Rouquette, S; Foucher, F; Audrain, O; Bouriel, C; Levêque, J

2010-02-01

The diagnosis of atypical epithelial hyperplasia (AEH) increases with breast cancer screening. AEH is divided in three groups: atypical ductal hyperplasia, columnar cell lesions with atypia, lobular neoplasia. The management of women with AEH is not consensual because of uncertainty about their diagnosis related to the type of the biopsy sampling (core needle biopsy or surgical excision) and their controversial clinical signification between risk marker and true precursor of breast cancer. A systematic review of published studies was performed. Medline baseline interrogation was performed with the following keywords: atypical ductal hyperplasia, columnar cell lesions with atypia, lobular neoplasia, core needle biopsy, breast cancer, precursor lesion, hormonal replacement therapy. For each breast lesion, identified publications (English or French) were assessed for clinical practise in epidemiology, diagnosis and patient management. With immunohistochemistry and molecular studies, AEH seems to be precursor of breast cancer. But, epidemiological studies show low rate of breast cancer in women with AEH. AEH were still classified as risk factor of breast cancer. Because of high rate of breast cancer underestimation, surgical excision is necessary after the diagnosis of AEH at core needle biopsy. Surgical oncology rules and collaboration with radiologist are required for this surgery. A second operation was not required due to involved margins by AEH (except with pleiomorphic lobular neoplasia) because local control of breast cancer seems to be unchanged. Besides, hormonal replacement therapy for patient with AEH is not recommended because of lack of studies about this subject. Copyright 2009 Elsevier Masson SAS. All rights reserved.

[A Case of Adenoma of the Nipple Suspected of Breast Cancer].

PubMed

Takada, Koji; Kashiwagi, Shinichiro; Goto, Wataru; Asano, Yuka; Morisaki, Tamami; Noda, Satoru; Takashima, Tsutomu; Onoda, Naoyoshi; Ohsawa, Masahiko; Hirakawa, Kosei; Ohira, Masaichi

2017-11-01

Adenoma of the nipple is a rare benign tumor, and it is important to distinguish from Paget's disease or breast cancer. A 45- year-old woman had found induration under the right areola before 2 months and visited our hospital. Ultrasonography showed a 2.4 cm solid tumor in a cystic lesion, which had high blood flow in E area of the right mammary gland. The tumor suspected as duct papillomatosis by core needle biopsy. No metastasis lesion was found by computed tomography and bone scintigraphy. But magnetic resonance imaging showed as a marginally clear tumor with contrast enhanced findings that were relatively early reinforced and prolonged. Because there was a possibility of malignancy based on these findings, tumorectomy was done with patient consent. Histological examination revealed usual ductal hyperplasia(duct papillomatosis)and no malignancy. No recurrence was seen for a year after operation. When diagnosing a tumor under areola, be careful not to misdiagnose malignancy.

[Bushen Huoxue Fang promotes the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia].

PubMed

Sun, Jie; Li, Qiu-Fen; Tian, Dai-Zhi; Jiang, Shao-Bo; Wu, Xian-De; Qiu, Shun-An; Ren, Xiao-Gang; Li, Yu-Bing

2014-09-01

To investigate the effects of Bushen Huoxue Fang (BSHX) on the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia (BPH) and its possible action mechanism. One hundred 3- month-old male Wistar rats were randomly divided into four groups of equal number (control, castrated, BPH model, and BSHX). BPH models were made by subcutaneous injection of testosterone following castration; the rats in the BSHX group were treated intragastrically with BSHX at 2.34 g/ml after modeling, while those in the other two groups with equal volume of saline, all for 37 days. On the 38th day, all the rats were sacrificed and their prostates harvested for detection of the distribution of TGF-beta1 and alpha-actin and the count of positive cells in the prostatic ductal system by immunohistochemical staining. The apoptosis rate of epithelial cells in the prostatic ductal system was determined by TUNEL assay. The expression of TGF-beta1 was significantly increased in the rats of the BSHX group as compared with the BPH models in both the proximal prostatic duct ([15.28 +/- 4.30]% vs [36.42 +/- 8.10]%, P < 0.01) and the distal prostatic duct ([4.42 +/- 2.07]% vs [8.71 +/- 2.28 ]%, P < 0.05), while the expression of alpha-actin in the proximal duct was remarkably higher in the BSHX-treated rats than in the models ([28.14 +/- 7.43]% vs [18.28 +/- 4.07]%, P < 0.01), but lower than in the control animals ([33.57 +/- 6.85]%, P < 0.05). Compared with the control group, the BPH models and BSHX-treated rats both exhibited markedly decreased apoptosis of epithelial cells in the proximal prostatic duct ([39.42 +/- 9.20]% vs [3.86 +/- 1.34]%, P < 0.01, and [31.14 +/- 5.64]%, P < 0.01) and distal prostatic duct ([17.60 +/- 4.86]% vs [3.07 +/- 1.14]%, P < 0.01, and [12.37 +/- 2.25]%, P < 0.05). The apoptosis rate of epithelial cells in the prostatic ductal system was significantly higher in the BSHX-treated rats than in the BPH models (P < 0.01). By upregulating the expression of TGF-beta, BSHX can suppress the reduction of smooth muscle cells in the proximal prostatic duct, promote the apoptosis of prostatic epithelial cells, and thus effectively inhibit benign prostatic hyperplasia.

S-(−)equol producing status not associated with breast cancer risk among low isoflavone consuming US postmenopausal women undergoing a physician recommended breast biopsy

PubMed Central

Virk-Baker, Mandeep K.; Barnes, Stephen; Krontiras, Helen; Nagy, Tim R.

2014-01-01

Soy foods are the richest sources of isoflavones, mainly daidzein and genistein. Soy isoflavones are structurally similar to the steroid hormone 17β-estradiol and may protect against breast cancer. S-(−)equol, a metabolite of the soy isoflavone daidzein, has a higher bioavailability and greater affinity for estrogen receptor-β than daidzein. About one third of the Western population is able to produce S-(−)equol, and the ability is linked to certain gut microbes. We hypothesized that the prevalence of breast cancer, ductal hyperplasia, and overall breast pathology will be lower among S-(−)equol producing, as compared to non -producing, postmenopausal women undergoing a breast biopsy. We tested our hypothesis using a cross-sectional study design. Usual diets of the participants were supplemented with one soy bar per day for three consecutive days. Liquid chromatography-multiple reaction ion monitoring mass spectrometry analysis of urine from 143 subjects revealed 25 (17.5%) as S-(−)equol producers. We found no statistically significant associations between S-(−)equol producing status and overall breast pathology (OR 0.68; 95% CI 0.23 – 1.89), ductal hyperplasia (OR 0.84; 95% CI 0.20 – 3.41), or breast cancer (OR 0.56; 95% CI 0.16 – 1.87). However, the mean dietary isoflavones intake was much lower (0.3 mg/day) than in previous reports. Given that the amount of S-(−)equol produced in the gut depends on the amount of daidzein exposure, the low soy intake coupled with lower prevalence of S-(−)equol producing status in the study population favors towards null associations. Findings from our study could be used for further investigations on S-(−)equol producing status and disease risk. PMID:24461312

Adenomatous ductal proliferation/hyperplasia in the parotid gland associated without any other pathological lesions; a report and survey of the literatures.

PubMed

Adhikari, Bhoj Raj; Nishimura, Michiko; Takimoto, Kosuke; Harada, Fumiya; Onishi, Aya; Hiraki, Daichi; Paudel, Durga; Neopane, Puja; Utsunomiya, Masafumi; Morikawa, Tetsuro; Yoshida, Koki; Sato, Jun; Shakya, Mamata; Nakayama, Eiji; Nagayasu, Hiroki; Abiko, Yoshihiro

2018-05-15

Adenomatous ductal proliferation/hyperplasia (ADP/H) is a rare hyperplastic condition of the salivary gland. It is mostly associated with other salivary gland pathologies such as tumors and inflammations, and is incidentally found in tissue sections during histopathological examinations of those diseases. Herein, we report a case of ADP/H in the parotid gland not associated with any other pathological lesions, and present a review of the literature on this condition. A 60-year-old Japanese female complained of swelling on the left side of parotid region. Clinical examination revealed a swelling on the lower lobe of the left parotid gland. The lesion was firm but non-tender and was not attached to adjacent structures. A clinical diagnosis of benign salivary gland tumor was reached, and surgical excision was performed under general anesthesia. Histopathological examination revealed an intact parotid gland capsule with isomorphic and basaloid cells within scanty cytoplasm. In addition, an admixture of hyperplasia and proliferation of the intercalated ducts, the presence of zymogen granules, the absence of solid nests, and a peripheral palisaded arrangement of the cells were observed. Based on these findings, a diagnosis of ADP/H was confirmed. ADP/H is a non-tumorous lesion; therefore, tumor involvement should be ruled out before the diagnosis is reached.

Benign Breast Disease Team Project — EDRN Public Portal

Cancer.gov

To identify women diagnosed with atypical ductal hyperplasia (ADH) who are at increased risk of developing invasive breast cancer (IBC) and who might benefit from risk reduction with the use of chemoprevention agents such as Tamoxifen. (Note: A companion protocol will study women with DCIS and their risk for invasive breast cancer.)

Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland

PubMed Central

Godde, Nathan J.; Sheridan, Julie M.; Smith, Lorey K.; Pearson, Helen B.; Britt, Kara L.; Galea, Ryan C.; Yates, Laura L.; Visvader, Jane E.; Humbert, Patrick O.

2014-01-01

Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression. PMID:24852022

Early Dysregulation of Cell Adhesion and Extracellular Matrix Pathways in Breast Cancer Progression

PubMed Central

Emery, Lyndsey A.; Tripathi, Anusri; King, Chialin; Kavanah, Maureen; Mendez, Jane; Stone, Michael D.; de las Morenas, Antonio; Sebastiani, Paola; Rosenberg, Carol L.

2009-01-01

Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand the relationship of breast lesions to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with estrogen receptor positive sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by quantitative real-time PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and extracellular matrix pathways, are dysregulated before invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches. PMID:19700746

[Diagnosis of flat epithelial atypia (FEA) after stereotactic vacuum-assisted biopsy (VAB) of the breast: What is the best management: systematic surgery for all or follow-up?].

PubMed

David, N; Labbe-Devilliers, C; Moreau, D; Loussouarn, D; Campion, L

2006-11-01

FEA lesions group two histological types: columnar cell hyperplasia with atypia (CCHA) and columnar cell change with atypia (CCA). The increasing use of VAB has resulted in increased detection of isolated FEA lesions. The aim of this study was to define the best management possible for these patients: which cases may not need excision? From our database of 780 VABs carried out from 2000 to 2004, 59 patients with FEA were diagnosed. Cases in which no surgery was performed or all features were not available were excluded, thus excluding 19 cases. Forty patients with FEA were included. We reviewed clinical and mammographic characteristics, histological biopsy, and the corresponding surgically excised tissue features. VAB yielded 25 cases of CCHA and 15 cases of CCA. Surgery revealed seven ductal carcinoma cases (four invasive, three in situ); nine benign lesions, and 24 with atypia (19 FEA and six atypical ductal hyperplasia). We found two features related to the risk of cancer: the presence and the size of hyperplasia. All carcinomas were found within the CCHA lesions. No cancer was yielded when size was less than 10 mm within CCA lesions and lesions that were totally removed. We recommend surgical excision when CCHA greater than 10 mm is found on the VAB or it is incompletely removed. CCA lesions or CCHA less than 10 mm or totally removed may obviate systematic surgery.

Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise or not. Results of a 5-year prospective study.

PubMed

Uzoaru, Ikechukwu; Morgan, Bradley R; Liu, Zheng G; Bellafiore, Frank J; Gaudier, Farah S; Lo, Jeanne V; Pakzad, Kourosh

2012-10-01

Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3,948 cases of breast CNB between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. There were 3.7 % (145/3,948) pure FEA and 1.5 % (58/3,948) concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, 46.2 % (67/145) had microcalcifications on mammography with 65.5 % (95/145) of patients undergoing subsequent excisional biopsies with the following findings: benign 20 % (19/95), ADH 37.9 % (36/95), ductal carcinoma in situ (DCIS) 1.1 % (1/95), and DCIS and invasive ductal carcinoma (IDC) 2.1 % (2/95). In the concomitant FEA and ADH group, 86.2 % (50/58) patients had microcalcifications on radiograph with 74.1 % (43/58) of patients undergoing subsequent excisions with: benign 23.3 % (10/43), DCIS 9.3 % (4/43), DCIS and IDC 4.7 % (2/43), DCIS + lobular carcinoma in situ + invasive lobular carcinoma 2.3 % (1/43), and tubular carcinoma 2.3 % (1/43). The incidence of carcinoma in the FEA + ADH group is 18.6 % (8/43) and 3.2 % (3/95) for the pure FEA group. This difference is statistically significant (p = 0.0016). The relative risk of carcinoma in the ADH + FEA group versus the pure FEA group is 6.4773, with 95 % CI of 1.8432 and 22.76 24. Five-year mean follow-up in the unexcised pure FEA did not show any malignancies. These findings suggest that pure FEA has a very low association with carcinoma, and these patients may benefit from close clinical and mammographic follow-up while the combined pure FEA and ADH cases may be re-excised.

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast].

PubMed

Oliveira, Agliberto Barbosa de; De Luca, Laurival Antônio; Carvalho, Grigna Teixeira; Arias, Victor Eduardo Arua; Carvalho, Lídia Raquel de; Assunção, Maria do Carmo

2004-01-01

Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

The Effects of Bisphenol A (BPA) on ErbB2 Positive Breast Cancer

DTIC Science & Technology

2010-11-01

development and progression. We have previously shown that either prenatal ( gestational days 10-21) only exposure to BPA or prepubertal (postpartum days...receptor (PR) in the mammary gland, and increased lateral branching (30). With gestational exposure alone, BPA has been reported to increase the...ductal hyperplasia and carcinoma in situ (32). Gestational exposure to BPA has been reported to result in reproductive and endocrine disruption in

Pathological criteria and practical issues in papillary lesions of the breast - a review.

PubMed

Ni, Yun-Bi; Tse, Gary M

2016-01-01

Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized. © 2015 John Wiley & Sons Ltd.

Atypical epithelial hyperplasia of the breast: state of the art.

PubMed

Dion, Ludivine; Racin, Adelaïde; Brousse, Susie; Beltjens, Françoise; Cauchois, Aurélie; Levêque, Jean; Coutant, Charles; Lavoué, Vincent

2016-09-01

Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA.

Isolation of Estrogen Regulated Genes from MCF-7 Human Mammary Cancer Cells

DTIC Science & Technology

1990-07-13

Syrian hamster BHK cells. The expression of approximately five hundred clones increased at various points in Gl transit (Hirschhom er d., 1984). No...hyperplasia of ductal epithelium of the mammary gland (Lyons etal., 1958). Biochemical changes in uterine wet weight, protein content, and nucleic... transition from a resting to a growing state (Kaufman and Sharp, 1983). Similarly post- transcriptional processing appears to be important in the ceU

Human Mammary Epithelial Cell Transformation by Rho GTPase through a Novel Mechanism

DTIC Science & Technology

2008-08-01

structures, termed the terminal ductal–lobular units (TDLUs), together with interlobular fat and fibrous tissue [16,17]. Most breast cancers arise in the...that benign stages (such as typical and atypical hyperplasia ), noninvasive cancers (such as carcinoma in situ – ductal or lobular), and invasive cancers... inflammatory breast cancer and overexpression of RhoC in immortalized hMECs induces their transformation (35). Impor- tantly, given the linkage of Rho

AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma

NASA Astrophysics Data System (ADS)

Rita, R.; Delyuzar; Laksmi, L. I.

2018-03-01

Benign prostatic hyperplasia and prostatic adenocarcinoma were common diseases and usually occurred after the 5th decade of life. The problem in diagnosing using Hematoxylin and Eosin staining was how to differentiate whether it is benign or malignant zone. Therefore, proliferating markers, such as AgNOR, could be helping to over this difficulty. A descriptive study using consecutive sampling as the method of sample recruiting was conducted to describe AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma. AgNOR staining was done in 13 benign prostatic hyperplasia samples and 7 prostatic adenocarcinoma samples, which have been confirmed using p63 immunohistochemical staining before. Benign prostatic hyperplasia usually showed lower AgNOR proliferating activity while all of theprostatic adenocarcinoma (100%) had high AgNOR proliferating activity.

Assessment of "grading" with Ki-67 and c-kit immunohistochemical expressions may be a helpful tool in management of patients with flat epithelial atypia (FEA) and columnar cell lesions (CCLs) on core breast biopsy.

PubMed

Tomasino, Rosa M; Morello, Vincenza; Gullo, Arianna; Pompei, Giancarlo; Agnese, Valentina; Russo, Antonio; Rinaldi, Gaetana

2009-11-01

It is essential to reach a better understanding of "flat epithelial atypia/columnar cell lesions" (FEA/CCLs) in breast core biopsies. Our aim was to explore their biological nature, in order to predict the likelihood of an upgrade to carcinoma. "Cytological grading" has been specially focused, in view of its possible utility in the choice of management. One hundred thirty of a total of 900 cases core needle (CN)/vacuum-assisted biopsies (VABs), with diagnoses of "hyperplasia" and "atypia" were retrospectively re-evaluated. Pathological findings of further excision biopsies (FEBs) performed in 40/75 patients with follow-up were compared with the previous diagnoses. In all cases, both Ki-67 and c-kit immunoreactivities were explored and compared with both normal breast tissues and subsequently documented cancers, with special reference to the hyperplastic FEA/CCLs, with "mild" atypia (FEA/CCHAm). Sixteen cases were re-diagnosed as "usual ductal hyperplasia" (UDH), 60 as "columnar cell hyperplasia" (CCH), and 54 as FEA/CCHA, 30 of which FEA/CCHAm and 24 FEA/CCHAh (with high atypia). Significantly, the Ki-67 index proved to be on the increase and c-kit expression on the decrease in FEA/CCHA lesions, mainly in the FEA/CCHAh group and in the subsequently observed cancers, compared with either benign tissues or the FEA/CCH cases. It was also significant that most of the carcinomas were found in FEBs within the FEA/CCHAh group. In this study cytological grading, together with Ki-67 and c-kit indices, proved to be helpful in FEA/CCLs evaluation. With regard to FEA/CCHAm lesions, an adequate surveillance appears to be a more appropriate management tool than FEB, as a result of their biological nature and behavior.

The Role of DNA Methyltransferase in the Progression of Breast Cancer of a Hormone Independent Phenotype

DTIC Science & Technology

1999-09-01

cycle with alternating rounds of proliferation and apoptosis. The greatest increase in mitotic index occurs during the luteal phase of the cycle...for the mitogenic actions of progesterone on breast tissue during the luteal phase of the reproductive cycle (72, 95). Progestins induce growth hormone...antagonist show ductal hyperplasia. Ablation of the GH/IGF1 axis in mice with human breast cancer xenografts, or transplant of xenografts into GH- deficient

Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma.

PubMed

Fan, Chuifeng; Zhao, Yang; Mao, Xiaoyun; Miao, Yuan; Lin, Xuyong; Jiang, Guiyang; Zhang, Xiupeng; Han, Qiang; Luan, Lan; Wang, Enhua

2014-11-01

Armadillo repeat-containing protein 8 (Armc8) is a key factor to regulate cell membrane adhesion complex through promoting α-catenin degradation. However, its expression and function in human malignant tumors are largely unknown. Here, we present our study investigating Armc8 expression in tumor and non-tumor breast tissues including 45 normal epithelia, 53 lesions of hyperplasia with or without dysplasia, 22 benign tumors, and 92 carcinomas including 28 carcinomas in situ and 64 infiltrating carcinomas using immunohistochemistry (IHC) and Western blotting study. Armc8 expression was detected mainly in the cytoplasm with occasional membrane immunostaining. The positive rate of Armc8 expression in normal breast epithelia (8.9%, four out of 45) was very low. No significant difference was found between Armc8 expression in usual ductal hyperplasia (UDH) (11.1%, two out of 18), benign breast tumors including intraductal papilloma (10.0%, one out of 10) and fibroadenoma (8.3%, one out of 12), and normal breast epithelia (p>0.05). Elevated expression of Armc8 was found in breast epithelia with dysplasia (24.0%, six out of 25) compared to that in normal breast epithelia, UDH, and benign breast tumors (p<0.05). Armc8 expression in breast carcinoma including breast carcinoma in situ (10/28, 35.7%), infiltrating ductal carcinoma (60.7%, 34/56), and infiltrating lobular carcinoma (50.0%, 4/8) was higher than that in normal breast epithelia, UDH, benign breast tumors, and breast epithelia with dysplasia (p<0.05). The highest expression of Armc8 was found in infiltrating breast carcinoma (59.4%, 38/64) compared to all the other breast tissues. Higher Armc8 expression was found to be linked to lymph node metastasis and advanced tumor-node-metastasis (TNM) stages (III+IV) in infiltrating breast carcinoma (p<0.05). We further confirmed Armc8 expression in breast epithelial cell line MCF10A and breast carcinoma cell lines including MCF-7, MDA-MB-231, and ZR751 using Western blotting and immunofluorescent study. These results indicate that the elevated expression of Armc8 may be involved in carcinogenesis including atypia-to-carcinoma progression and cancer development of breast carcinoma.

Estrogen Receptor Expression in Atypical Hyperplasia: Lack of Association with Breast Cancer

PubMed Central

Barr Fritcher, Emily G.; Degnim, Amy C.; Hartmann, Lynn C.; Radisky, Derek C.; Boughey, Judy C.; Anderson, Stephanie S.; Vierkant, Robert A.; Frost, Marlene H.; Visscher, Daniel W.; Reynolds, Carol

2011-01-01

Background Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. Methods ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967–1991. The ACISRIII (Dako, Carpinteria, CA) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared to the Iowa SEER control population. Results Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity [p<0.05]. ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. Conclusion We found increasing ER expression in atypical hyperplasia with increasing age. ER expression in atypical hyperplasia does not further discriminate breast cancer risk in women with atypia. PMID:21209395

Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis

PubMed Central

Jones, Huw B; Reens, Jaimini; Brocklehurst, Simon R; Betts, Catherine J; Bickerton, Sue; Bigley, Alison L; Jenkins, Richard P; Whalley, Nicky M; Morgan, Derrick; Smith, David M

2014-01-01

Antagonism of the effects of glucagon as an adjunct therapy with other glucose-lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α-cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice (PC2-ko), in which α-cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2-ko and wild-type (WT) mice were maintained drug-free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2-ko animals displayed marked changes in islet morphology from α-cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6–8 months. Islet hyperplasias and tumours primarily consisted of α-cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α-cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2-ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis. PMID:24456331

Flat epithelial atypia of the breast: characteristics and behaviors.

PubMed

Sudarshan, Monisha; Meguerditchian, Ari-Nareg; Mesurolle, Benoit; Meterissian, Sarkis

2011-02-01

Flat epithelial atypia (FEA) increasingly is being recognized as a pathologic entity on core needle biopsies. However, definitive management of this columnar cell lesion remains debatable because its malignant potential is unknown. A PubMed search for "flat epithelial atypia" and "columnar cell lesions" was performed. FEA commonly was encountered in the background of higher-grade lesions such as atypical ductal hyperplasia, ductal carcinoma in situ, and tubular and lobular carcinomas. Its molecular and cytogenetic profile revealed some alterations similar to precancerous lesions. Pure FEA on core needle biopsies was upgraded to higher-grade lesions on subsequent surgical excision. Current management of FEA is best achieved through a multidisciplinary review considering various factors to determine if surgical excision is warranted. Further studies are required to elucidate the malignant potential of this columnar cell lesion. Copyright © 2011 Elsevier Inc. All rights reserved.

Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT

PubMed Central

Dong, Aisheng; Wang, Yang; Lu, Jianping; Zuo, Changjing

2016-01-01

Abstract Interpretation of 18F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. PMID:26975010

Spontaneous necrotizing sialometaplasia of the submandibular salivary gland in a Beagle dog

PubMed Central

Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

2015-01-01

A single mass was found on the left submandibular salivary gland at necropsy of a 15-month-old male commercially bred laboratory Beagle dog from a control dose group from a repeat toxicity study. Microscopically, the mass was composed of a well-demarcated area of coagulative necrosis surrounded and separated from the normal salivary gland tissue by a thick fibrovascular capsule. Necrosis was admixed with areas of hemorrhage, fibrin, edema, fibrinoid necrosis of the vascular tunica media, and thrombosis of small and large vessels. Within the necrotic tissue, there was marked ductal hyperplasia, and squamous metaplasia of duct and acinar epithelium. The mass was diagnosed as necrotizing sialometaplasia of the submandibular gland. Hyperplastic ductal elements and squamous metaplasia can be mistaken microscopically with squamous cell carcinoma. Therefore, pathologists should be aware of this lesion as to avoid errors in the diagnosis of this benign pathologic condition. PMID:26441480

Spontaneous necrotizing sialometaplasia of the submandibular salivary gland in a Beagle dog.

PubMed

Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

2015-07-01

A single mass was found on the left submandibular salivary gland at necropsy of a 15-month-old male commercially bred laboratory Beagle dog from a control dose group from a repeat toxicity study. Microscopically, the mass was composed of a well-demarcated area of coagulative necrosis surrounded and separated from the normal salivary gland tissue by a thick fibrovascular capsule. Necrosis was admixed with areas of hemorrhage, fibrin, edema, fibrinoid necrosis of the vascular tunica media, and thrombosis of small and large vessels. Within the necrotic tissue, there was marked ductal hyperplasia, and squamous metaplasia of duct and acinar epithelium. The mass was diagnosed as necrotizing sialometaplasia of the submandibular gland. Hyperplastic ductal elements and squamous metaplasia can be mistaken microscopically with squamous cell carcinoma. Therefore, pathologists should be aware of this lesion as to avoid errors in the diagnosis of this benign pathologic condition.

Development of Spontaneous Mammary Tumors in BALB/c-p53+/-Mice: Detection of Early Genetic Alterations and the Mapping of BALB/c Susceptibility Genes

DTIC Science & Technology

2005-07-01

type allele in the sample, with one being a papillary ductal study used all BALB/c female mice; therefore, both strain and gender hyperplasia and the...other being a solid adenocarcinoma but with a could be contributing to the difference in LOH frequency. To deter- significant fibrous stromal...Intracytoplasmic granular staining in the epithelium was the most common pattern of staining and was regarded as positive. Imm unoreactivity in inflammatory

Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

PubMed Central

MacGrogan, Gaëtan; Mathoulin-Pélissier, Simone; Vincent-Salomon, Anne; Soubeyran, Isabelle; Picot, Véronique; Coindre, Jean-Michel; Mauriac, Louis

2007-01-01

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer. PMID:17551752

Epithelial atypia in biopsies performed for microcalcifications. practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up.

PubMed

de Mascarel, Isabelle; MacGrogan, Gaëtan; Mathoulin-Pélissier, Simone; Vincent-Salomon, Anne; Soubeyran, Isabelle; Picot, Véronique; Coindre, Jean-Michel; Mauriac, Louis

2007-07-01

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer.

Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland.

PubMed

Zhang, Jian; Sun, Yibin; Liu, Yunhai; Sun, Yi; Liao, Dezhong Joshua

2004-10-01

Many studies have suggested that elevated estrogens and androgens may be etiologically related to the development of breast cancer, endometrial cancer and uterine leiomyomas. We and other investigators have previously shown that estrogen and androgen are synergistic in the induction of mammary carcinogenesis in the Noble rat. However, the mechanisms behind the synergy is unknown, and it is unclear whether such synergy is unique for the Noble rat and for the mammary gland. In this study we treated female FVB mice with 17beta-estradiol (E2) and 5alpha-dihydrotestosterone-bezonate (DHT-B), alone and in combination, using silastic tubing for 2-7 months. The results showed that DHT-B alone induced proliferation of uterine endometrial epithelium and myometrial smooth muscle cells, whereas E2 alone induced much more pronounced growth of endometrial epithelium without affecting smooth muscle cells. Combined treatment with E2+DHT-B caused an even more severe hyperplasia of endometrial epithelium and myometrial muscle cells, compared with the treatment with each hormone alone. Uterine leiomyomas were observed in 2 of 6 mice at 7 months of combined treatment but not in any of 6 or 7 mice receiving each single hormone. DHT-B alone induced growth and secretion of mammary ductal cells, as well as growth of mammary stroma. E2 alone stimulated much more pronounced growth of both ductal cells and alveolar cells and secretion of alveolar cells, but had no effect on mammary stroma. Treatment with both E2 and DHT-B caused more severe hyperplasia of mammary ducts and alveoli, compared to the treatment with each hormone alone. Intraductal hyperplasia occurred early and frequently in the E2+DHT-B- treated mice, but no mammary tumors were observed. These results suggest that E2 and DHT-B have synergistic effects on the growth of uterine endometrial epithelium and myometrial muscle cells, as well as mammary epithelial ducts and alveoli.

A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling.

PubMed

Miret, Noelia; Rico-Leo, Eva; Pontillo, Carolina; Zotta, Elsa; Fernández-Salguero, Pedro; Randi, Andrea

2017-11-01

Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05μM HCB induced cell migration and TGF-β1 signaling, whereas 5μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR+/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR+/+ mice. Primary culture of mammary epithelial cells from AhR+/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5μM). Interestingly, AhR-/- mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds. Copyright © 2017. Published by Elsevier Inc.

The breast lesion excision system (BLES) A preliminary experience.

PubMed

Citgez, Bulent; Atay, Murat; Yetkin, Gu Rkan; Kartal, Abdulcabbar; Mihmanli, Mehmet; Uludag, Mehmet

2016-01-01

BLES (Intact Breast lesion Excision System) is a new defined system which can remove the lesion completely. We aimed to evaluate and compare the results of BLES used for breast lesions requiring histological verification with other percutaneous biopsy methods in the literature. Patients with breast lesions smaller than 20mm and for whom biopsy was indicated were involved in the study. 18(1 male, 17 female, mean age: 41. 83, age range: 26-72) patients were included the study. BLES is applied with a single insertion. Radiofrequency is used to excise the breast tissue after the insertion. Around the lesion, tissue capture basket is moved back and forth. Once captured, the basket and the probe is removed from the incision area. All of the lesions were excised en-bloc. The only complication occured was subdermal hematoma in one case (5.5%) which resolved spontenously. Pathological analysis of the specimens revealed 9 fibroadenoma, 3 fibroadenomatosis hyperplasia, 3 complicated and calcified cysts, 1 ductal epithelial hyperplasia, 1 carcinoma in situ with intraductal papillary carcinoma focus and 1 ductal carcinoma in situ with 2 mm invasive carcinoma focus. The last two cases underwent resectıon and sentınal lymph node procedure. BLES is a is non-invasive method which has no need for additional initiatives in benign cases, provide sufficient samples for pathological diagnosis and remove the lesion in one piece. BLES method can be applied in selected cases. Breast Lesion Excision System, Breast, Biopsy, Radiofrequency, Lesion.

Personal history of proliferative breast disease with atypia and risk of multifocal breast cancer.

PubMed

Nutter, Ellen L; Weiss, Julia E; Marotti, Jonathan D; Barth, Richard J; Eliassen, M Scottie; Goodrich, Martha E; Petersen, Curtis L; Onega, Tracy

2018-04-01

A history of proliferative breast disease with atypia (PBDA) may be indicative of an increased risk not just of breast cancer but also of a more aggressive form of breast cancer. Multifocal breast cancer (MFBC), defined as 2 or more tumors in the same breast upon a diagnosis of cancer, is associated with a poorer prognosis than unifocal (single-tumor) breast cancer. PBDA, including atypical ductal hyperplasia and atypical lobular hyperplasia, is a known risk factor for breast cancer. Using New Hampshire Mammography Network data collected for 3567 women diagnosed with incident breast cancer from 2004 to 2014, this study assessed the risk of MFBC associated with a previous diagnosis of PBDA. Women with a history of PBDA were found to be twice as likely to be subsequently diagnosed with MFBC as women with no history of benign breast disease (BBD; odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61). Ductal carcinoma in situ on initial biopsy was associated with a 2-fold increased risk of MFBC in comparison with invasive cancer (OR, 2.13; 95% CI, 1.58-2.88). BBD and proliferative BBD without atypia were not associated with MFBC. Women with a history of previous PBDA may be at increased risk for MFBC. Women with a history of PBDA may benefit from additional presurgical clinical workup. Cancer 2018;124:1350-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

Ensuring excision of intraductal lesions: marker placement at time of ductography.

PubMed

Woodward, Suzanne; Daly, Caroline P; Patterson, Stephanie K; Joe, Annette I; Helvie, Mark A

2010-11-01

To propose grid coordinate marker placement for patients with suspicious ductogram findings occult on routine workup. To compare the success of marker placement and wire localization (WL) with ductogram-guided WL. A retrospective search of radiology records identified all patients referred for ductography between January 2001 and May 2008. Results for 16 patients referred for ductogram-guided WL and 5 patients with grid coordinate marker placement at the time of ductography and subsequent WL were reviewed. Surgical pathology results and clinical follow-up were reviewed for concordance. Nine of 16 patients (56.3%) underwent successful ductogram-guided WL. Eight of nine patients had papillomas, one of which also had atypical ductal hyperplasia (ADH). One of nine patients had ectatic ducts with inspisated debris. Seven patients who failed ductogram-guided WL eventually underwent open surgical biopsy. Four of seven patients had papillomas, one of which also had lobular carcinoma in situ. Remaining patients had ADH (1/7) and fibrocystic changes with chronic inflammation (3/7). All five (100%) patients with grid coordinate marker placement underwent successful WL and marker excision. Pathology results included three papillomas, papillary intraductal hyperplasia, and fibrocystic change. Grid coordinate marker placement at the time of abnormal ductogram provided an accurate method of localizing ductal abnormalities that are occult on routine workup, thus facilitating future WL. Marker placement obviated the need for repeat ductogram on the day of surgery and ensured surgical removal of the ductogram abnormality. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia on Needle Biopsy.

PubMed

Menes, Tehillah S; Kerlikowske, Karla; Lange, Jane; Jaffer, Shabnam; Rosenberg, Robert; Miglioretti, Diana L

2017-01-01

Atypical ductal hyperplasia (ADH) is a known risk factor for breast cancer. Published risk estimates are based on cohorts that included women whose ADH was diagnosed before widespread use of screening mammograms and did not differentiate between the methods used to diagnose ADH, which may be related to the size of the ADH focus. These risks may overestimate the risk in women with presently diagnosed ADH. To examine the risk of invasive cancer associated with ADH diagnosed using core needle biopsy vs excisional biopsy. A cohort study was conducted comparing the 10-year cumulative risk of invasive breast cancer in 955 331 women undergoing mammography with and without a diagnosis of ADH. Data were obtained from 5 breast imaging registries that participate in the National Cancer Institute-funded Breast Cancer Surveillance Consortium. Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Ten-year cumulative risk of invasive breast cancer. The sample included 955 331 women with 1727 diagnoses of ADH, 1058 (61.3%) of which were diagnosed by core biopsy and 635 (36.8%) by excisional biopsy. The mean (interquartile range) age of the women at diagnosis was 52.6 (46.9-60.4) years. From 1996 to 2012, the proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten years following a diagnosis of ADH, the cumulative risk of invasive breast cancer was 2.6 (95% CI, 2.0-3.4) times higher than the risk in women with no ADH. Atypical ductal hyperplasia diagnosed via excisional biopsy was associated with an adjusted hazard ratio (HR) of 3.0 (95% CI, 2-4.5) and, via core needle biopsy, with an adjusted HR of 2.2 (95% CI, 1.5-3.4). Ten years after an ADH diagnosis, an estimated 5.7% (95% CI, 4.3%-10.1%) of the women had a diagnosis of invasive cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk (6.7%; 95% CI, 3.0%-12.8%) compared with those with ADH diagnosed via core needle biopsy (5%; 95% CI, 2.2%-8.9%). Current 10-year risks of invasive breast cancer after a diagnosis of ADH may be lower than those previously reported. The risk associated with ADH is slightly lower for women whose ADH was diagnosed by needle core biopsy compared with excisional biopsy.

Association of serum interleukin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases

PubMed Central

Lv, Zhuangwei; Liu, Min; Shen, Jinghui; Xiang, Dong; Ma, Yunfeng; Ji, Yanhong

2018-01-01

Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects. IL-10, IL-17A and TGF-α levels were measured using ELISA. Serum levels of these cytokine in patients with different breast diseases were evaluated. Furthermore, correlations between levels of these cytokines and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in ductal carcinoma were determined. The results demonstrated that serum levels of IL-10 and IL-17A were significantly increased in subjects with atypical hyperplasia and ductal carcinoma. Furthermore, IL-10 and IL-17A levels were increased in patients with a more serious clinical tumor stage and tumors that were ER− and PR−. Furthermore, high serum levels of TGF-α were associated with HER2+ tumors. A strong positive correlation was identified between TGF-α and IL-17A levels. Therefore, the results of the current study revealed that elevated serum IL-10, IL-17A and TGF-α levels are strongly associated with ductal carcinoma, specifically with tumor stage. High serum levels of IL-10 and IL-17A were also associated with the negative expression of ER and PR in ductal carcinoma, and high serum levels of TGF-α were associated with the positive expression of HER2 in ductal carcinoma. Thus, serum cytokine levels may be measured to identify patients with a poor prognosis who may benefit from more aggressive management and treatment. PMID:29904427

Association of serum interleukin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases.

PubMed

Lv, Zhuangwei; Liu, Min; Shen, Jinghui; Xiang, Dong; Ma, Yunfeng; Ji, Yanhong

2018-06-01

Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects. IL-10, IL-17A and TGF-α levels were measured using ELISA. Serum levels of these cytokine in patients with different breast diseases were evaluated. Furthermore, correlations between levels of these cytokines and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in ductal carcinoma were determined. The results demonstrated that serum levels of IL-10 and IL-17A were significantly increased in subjects with atypical hyperplasia and ductal carcinoma. Furthermore, IL-10 and IL-17A levels were increased in patients with a more serious clinical tumor stage and tumors that were ER - and PR - . Furthermore, high serum levels of TGF-α were associated with HER2 + tumors. A strong positive correlation was identified between TGF-α and IL-17A levels. Therefore, the results of the current study revealed that elevated serum IL-10, IL-17A and TGF-α levels are strongly associated with ductal carcinoma, specifically with tumor stage. High serum levels of IL-10 and IL-17A were also associated with the negative expression of ER and PR in ductal carcinoma, and high serum levels of TGF-α were associated with the positive expression of HER2 in ductal carcinoma. Thus, serum cytokine levels may be measured to identify patients with a poor prognosis who may benefit from more aggressive management and treatment.

The clinical use of a P63/cytokeratin7/18/cytokeratin5/14 antibody cocktail in diagnostic breast pathology.

PubMed

Reisenbichler, Emily S; Ross, John R; Hameed, Omar

2014-12-01

An antibody cocktail directed against p63, cytokeratin (CK)5/14, and CK7/18 is reported to be useful in distinguishing noninvasive from invasive breast lesions and for the characterization of intraductal epithelial proliferations. However, limited studies evaluate its use in clinical practice. A retrospective review of breast material at a university medical center identified cases that were immunostained with the above antibody cocktail. Additional p63 immunostaining alone was performed to further determine the utility of the antibody cocktail in the evaluation of invasion. Of 50 breast cases identified, the antibody cocktail was used to confirm or exclude invasion in 44 (88%). Twenty-two (50%) of these had easily identifiable p63/CK5/14-positive myoepithelial cells, whereas the remainder lacked such staining, confirming the diagnosis of invasive carcinoma. In 27 cases with available diagnostic material for additional p63 immunostaining, the cocktail better highlighted myoepithelial cells by staining nuclei and cytoplasm. Easier identification of invasion was also facilitated by CK7/18 expression in invasive foci, especially those composed of single cells. Ten cases were immunostained to help determine the nature of an intraductal proliferation. The cocktail demonstrated a mosaic staining pattern of both CK7/18- and CK5/14-positive epithelial cells in 3 (30%) cases consistent with usual hyperplasia; homogenous CK7/18 expression in the remaining cases supported the diagnosis of atypical ductal hyperplasia or carcinoma in situ. In summary, the p63/CK7/18/CK5/14 cocktail stain appears to be a useful tool in diagnostic breast pathology, in the evaluation of possible invasion, particularly in the setting of minute foci of invasion as well as in epithelial proliferations. Copyright © 2014 Elsevier Inc. All rights reserved.

Experimental study on the clinical effects of Xiaoru Sanjie Jiaonang on mammary glands hyperplasia and ki-67

PubMed Central

Zheng, Zi-Hao; Liu, Lin; Zou, Shi-Fang; Xu, Yu-Ting; Chen, Cui-Cui; Liang, Wen-Long; Guo, Bao-Liang; Wang, Yu; Zhu, Kai-Yuan; Liu, Jie-Na; Xu, Dan-Dan; Wang, Ji-Yan; Lin, Jia-Yan; Liu, Li; Zhang, Jian Guo; Chen, Xi

2018-01-01

Objective: This study aims to observe the effect and mechanism of Xiaoru Sanjie Jiaonang (XRSJ) on the treatment of mammary gland hyperplasia, and provide a theoretical basis and clinical evidence for clinical expansion. Methods: Japanese white rabbits were randomly divided into three groups: high-, middle- and low-dose groups; Xiaoyao Pill group; model control group; normal control group. The observation points were as follows: before XRSJ administration, three months after XRSJ administration, and three months after XRSJ discontinuance. Changes in breast height, morphological changes of the mammary gland under a light and electron microscope, and the expression of ki-67 were observed. At the same time, patients diagnosed with mammary gland hyperplasia at an Outpatient Clinic were selected and divided into treatment groups. These patients received XRSJ and Xiaoyao Pills, respectively, for one month, while patients in the control group did not receive any drug treatment. Clinical efficacy was observed while rechecking at the Outpatient Clinic after three months. Treatment with a therapeutic dose of XRSJ could significantly reduce breast height, decrease the number of lobules and acini in hyperplastic mammary glands and the layer number of ductal glandular epithelial cells, substantially lower the content of serum estradiol (E2), significantly downregulate the expression of ki-67 protein in mammary tissues, and inhibit mammary gland hyperplasia. Conclusion: XRSJ treatment can relieve mammary tissue hyperplastic lesions, reduce E2 levels and downregulate the expression of ki-67. It has a significant therapeutic effect on mammary gland hyperplasia. PMID:29636873

Biological and genetic properties of the p53 null preneoplastic mammary epithelium

NASA Technical Reports Server (NTRS)

Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

2002-01-01

The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

Predictors of invasive breast cancer in mammographically detected microcalcification in patients with a core biopsy diagnosis of flat epithelial atypia, atypical ductal hyperplasia or ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy.

PubMed

Catteau, Xavier; Simon, Philippe; Noël, Jean-Christophe

2012-04-15

15±30% of malignancies detected through screening programs are ductal carcinoma in situ (DCIS), and the majority of DCIS cases present in the form of mammographic microcalcification. This study was performed in order to determine the value of features in predicting invasive disease in patients with mammographic calcification and to help determine which patients (with, Core Needle Biopsy-diagnosed DCIS) are the most appropriate candidates for Sentinel Lymph Node (SLN) biopsy. The original aspect of this study was to select patients with mammographic microcalcification but without an associated mass. The factor that we identified to be associated with invasive disease at final surgical excision was the presence of necrosis at core histology. SLN biopsy or complete axillary lymph node dissection was performed in 22 (40%) patients of whom only one (4.5%) had a micrometastasis. Further larger studies are needed to see if it would be interesting to propose a SLN biopsy in case of necrosis on CNB-diagnosed DCIS with microcalcifications but not associated with a mass. Copyright © 2012 Elsevier GmbH. All rights reserved.

Do breast columnar cell lesions with atypia need to be excised?

PubMed

Datrice, Nicole; Narula, Navneet; Maggard, Melinda; Butler, John; Hsiang, David; Baick, Choong; Lane, Karen

2007-10-01

Columnar cell lesion with atypia (CCLA) is a newly recognized pathologic entity seen in breast specimens. The breast cancer risk associated with this finding is unclear, although CCLA had been found adjacent to both in situ and invasive carcinomas, but the incidence is unknown. Breast specimens from patients with a columnar cell lesion were reviewed by a pathologist for atypia. Twenty-one specimens with CCLA were identified [core biopsy (8), excisional biopsy (11), and simple mastectomy (2)]. Six of eight specimens with CCLA on core had adjacent abnormal pathology: infiltrating ductal carcinoma (IDC)/lobular carcinoma in situ (LCIS) (1), ductal carcinoma in situ (DCIS)/LCIS (1), DCIS (1), LCIS (1), and papillomatosis (2). Five of 11 specimens with CCLA on excisional biopsy had adjacent abnormal pathology: IDC (3), DCIS/LCIS (1), and atypical ductal hyperplasia/papilloma (1). Two of two simple mastectomy specimens had CCLA associated with IDC (1) and DCIS (1). Overall, abnormal pathology was found adjacent to CCLA in 62 per cent of specimens (13/21). Breast pathologic specimens containing a columnar cell lesion should be carefully examined for atypia. Surgical excision is warranted for CCLA found on core biopsy. The future risk of breast cancer based on the finding of CCLA alone requires further investigation.

Heterogeneity of keratin expression and actin distribution in benign and malignant mammary diseases.

PubMed

Wada, T; Yasutomi, M; Yamada, K; Hashimura, K; Kunikata, M; Tanaka, T; Huang, J W; Mori, M

1991-01-01

Immunoreactivity of monoclonal anti-cytokeratin KL1, PKK1, K8.12 and anti-actin antibodies in 101 cases of diseased human breast lesions showed irregular keratin distribution in luminal cells of terminal ductal-lobular unit and basal layer cells of the interlobular and main duct. Actin staining was confined to myoepithelial cells. Benign lesions showed great heterogeneity in luminal cells of the terminal ductal-lobular units. Breast carcinoma showed a reduced staining for keratins, heterogeneity of keratin expression was found in solid tubular carcinoma, and actin was usually absent: however, papillo-ductal or comedo type had actin positive myoepithelial cells around carcinoma foci.

Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study.

PubMed

Allison, Kimberly H; Rendi, Mara H; Peacock, Sue; Morgan, Tom; Elmore, Joann G; Weaver, Donald L

2016-12-01

This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast. Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power. The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. © 2016 John Wiley & Sons Ltd.

Histologic Features associated with Diagnostic Agreement in Atypical Ductal Hyperplasia of the Breast: Illustrative Cases from the B-Path Study

PubMed Central

Allison, Kimberly H.; Rendi, Mara H.; Peacock, Sue; Morgan, Tom; Elmore, Joann G.; Weaver, Donald L.

2016-01-01

Background Case specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast are poorly understood. Methods Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histologic features which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists’ perceptions of case difficulty, borderline features, or if they would obtain a second opinion were also examined for associations with agreement. Results Of the 2,070 participant interpretations on the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (p < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (p < 0.001). Diagnostic agreement ranged from 10–89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytologic monotony were associated with higher agreement. Lower agreement rates were associated with solid or micro-papillary architecture, borderline cytologic monotony or cases without a diagnostic area that was obvious on low power. Conclusions The results of this study suggest that pathologists frequently recognize the challenge of ADH cases with some cases more prone to diagnostic variability. In addition, there are specific histologic features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. PMID:27398812

Intravascular papillary endothelial hyperplasia of the foot.

PubMed

Cisco, R W; McCormac, R M

1994-01-01

Intravascular papillary endothelial hyperplasia is a rare benign reactive lesion usually found in thrombosed subcutaneous blood vessels. The lesion resembles malignant angiosarcoma clinically and histopathologically, and must be diagnosed correctly to avoid inappropriate treatment. The following is a case presentation involving the foot.

Maxillary sinus marrow hyperplasia in sickle cell anemia.

PubMed

Fernandez, M; Slovis, T L; Whitten-Shurney, W

1995-11-01

Marrow hyperplasia is a sequela of sickle cell anemia (SCA) and may be seen in the skull in children after 5 years of age [1]. The facial bones, except for the mandible and orbits, are usually not involved [1-3]. We report an unusual case of a 28-month-old black boy with SCA who presented with extensive marrow hyperplasia of the maxillary sinuses in addition to severe calvarial and mandibular changes. The imaging characteristics on CT (similar to other sites of marrow hyperplasia) and MR (low signal on both T1 and T2 sequences) should aid in making the correct diagnosis.

All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision.

PubMed

de Mascarel, Isabelle; Brouste, Véronique; Asad-Syed, Maryam; Hurtevent, Gabrielle; Macgrogan, Gaëtan

2011-09-01

The necessity of excision is debatable when atypia are diagnosed at stereotactic vacuum-assisted breast biopsy (microbiopsy). Among the 287 surgical excisions performed at Institut Bergonié from 1999 to 2009, we selected a case-control study group of 151 excisions; 52 involving all the diagnosed cancers and 99 randomly selected among the 235 excisions without cancer, following atypical microbiopsy (24 flat epithelial atypia; 50 atypical ductal hyperplasia; 14 lobular neoplasia; 63 mixed lesions). Mammographical calcification (type, extension, complete removal) and histological criteria of epithelial atypia (type, number of foci, size/extension), topography and microcalcification extension at microbiopsy were compared according to the presence or absence of cancer at excision. Factors associated with cancer at excision were Breast Imaging Reporting and Data System (BI-RADS5) lesions, large and/or multiple foci of mammographical calcifications, histological type, number, size and extension of atypical foci. Flat epithelial atypia alone was never associated with cancer at excision. BI-RADS5, atypical ductal hyperplasia (alone or predominant) and >3 foci of atypia were identified as independent pejorative factors. There was never any cancer at excision when these pejorative factors were absent (n=31). Presence of one (n=59), two (n=23) or three (n=14) factors was associated with cancer in 24, 15 and 13 cases with an odds ratio=5.8 (95% CI: 3-11.2) for each additional factor. We recommend that mammographical data and histological characteristics be taken into account in the decision-making process after diagnosis of atypia on microbiopsy. With experienced senologists and strict histological criteria, some patients could be spared surgery resulting in significant patient, financial and time advantages.

Flat Epithelial Atypia: Upgrade Rates and Risk-Stratification Approach to Support Informed Decision Making.

PubMed

Lamb, Leslie R; Bahl, Manisha; Gadd, Michele A; Lehman, Constance D

2017-12-01

Our aim was to determine upgrade rates of pure flat epithelial atypia (FEA) to malignancy and higher-risk lesions and to identify patients with FEA at low risk for upgrade. Medical chart review from 2007 to 2016 identified 208 consecutive patients with pure FEA diagnosed by image-guided core needle biopsy who underwent surgical excision (96.2% [200 of 208]) or had at least 2 years of imaging follow-up (3.8% [8 of 208]). Medical records were reviewed for risk factors and surgical outcomes. Overall upgrade rate of FEA to malignancy was 2.4% (5 of 208). All 5 upgraded cases were ductal carcinoma in situ at operation. The upgrade rate to atypical ductal hyperplasia, lobular carcinoma in situ, or atypical lobular hyperplasia was 29.8% (62 of 208). The FEA lesions in patients with a genetic mutation were more likely to upgrade to malignancy than FEA lesions in patients without a genetic mutation (33.3% [1 of 3] vs 2.0% [4 of 205]; p < 0.01). The FEA lesions in patients with a personal history of breast cancer were more likely to upgrade to higher-risk lesions than those without a personal history (47.8% [11 of 23] vs 27.6% [51 of 185]; p = 0.046) but were not more likely to be upgraded to malignancy (0% [0 of 23] vs 2.7% [5 of 185]; p = 0.42). The overall risk of upgrade of FEA to malignancy is low at 2.4%; however, the upgrade rate to a higher-risk lesion is nearly 30%. Surveillance rather than surgical excision of FEA can be a reasonable option for patients without a genetic mutation who opt against chemoprevention. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Physiological Levels of Pik3ca H1047R Mutation in the Mouse Mammary Gland Results in Ductal Hyperplasia and Formation of ERα-Positive Tumors

PubMed Central

Tikoo, Anjali; Roh, Vincent; Montgomery, Karen G.; Ivetac, Ivan; Waring, Paul; Pelzer, Rebecca; Hare, Lauren; Shackleton, Mark; Humbert, Patrick; Phillips, Wayne A.

2012-01-01

PIK3CA, the gene coding for the p110α subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers. To better understand the role of mutant PIK3CA in the initiation and/or progression of breast cancer, we have generated mice with a conditional knock-in of the common activating mutation, Pik3caH1047R, into one allele of the endogenous gene in the mammary gland. These mice developed a ductal anaplasia and hyperplasia by 6 weeks of age characterized by multi-layering of the epithelial lining of the mammary ducts and expansion of the luminal progenitor (Lin−; CD29lo; CD24+; CD61+) cell population. The Pik3caH1047R expressing mice eventually develop mammary tumors with 100% penetrance but with a long latency (>12 months). This is significantly longer than has been reported for transgenic models where expression of the mutant Pik3ca is driven by an exogenous promoter. Histological analysis of the tumors formed revealed predominantly ERα-positive fibroadenomas, carcinosarcomas and sarcomas. In vitro induction of Pik3caH1047R in immortalized mammary epithelial cells also resulted in tumor formation when injected into the mammary fat pad of immunodeficient recipient mice. This novel model, which reproduces the scenario of a heterozygous somatic mutation occurring in the endogenous PIK3CA gene, will thus be a valuable tool for investigating the role of Pik3caH1047R mutation in mammary tumorigenesis both in vivo and in vitro. PMID:22666336

Inhibition of benzo(a)pyrene-induced mammary carcinogenesis by retinyl acetate. [Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCormick, D.L.; Burns, F.J.; Albert, R.E.

1981-03-01

The administration of a 250-ppM retinyl acetate dietary supplement for various periods relative to intragastric administration of 50 mg benzo(a)pyrene (BP) significantly inhibited the induction of mammary cancers in virgin female inbred LEW/Mai rats. With day of BP administration taken as time 0, groups receiving the retinoid from weeks -2 to +1, +1 to +90, +20 to +90, and -2 to +90 showed a significant reduction in tumor response as compared to controls. The inhibition of carcinogenesis achieved by a +1 to +20 administration schedule was temporary. A 2-week exposure to supplemental retinyl acetate significantly reduced the mammary gland parenchymalmore » cell labeling index in ductal, alveolar, and terminal end bud structures. Beginning the retinyl acetate supplement 1 week after the administration of BP significantly reduced the number of terminal ductal hyperplasias. The inhibition of carcinogenesis achieved by a short period of retinyl acetate administration before and during the period of carcinogen availability as well as the inhibition achieved by long-term postcarcinogen retinoid exposure may involve an antiproliferative effect on the rat mammary gland.« less

Stratification of breast cancer risk in women with atypia: a Mayo cohort study.

PubMed

Degnim, Amy C; Visscher, Daniel W; Berman, Hal K; Frost, Marlene H; Sellers, Thomas A; Vierkant, Robert A; Maloney, Shaun D; Pankratz, V Shane; de Groen, Piet C; Lingle, Wilma L; Ghosh, Karthik; Penheiter, Lois; Tlsty, Thea; Melton, L Joseph; Reynolds, Carol A; Hartmann, Lynn C

2007-07-01

Atypical hyperplasia is a well-recognized risk factor for breast cancer, conveying an approximately four-fold increased risk. Data regarding long-term absolute risk and factors for risk stratification are needed. Women with atypical hyperplasia in the Mayo Benign Breast Disease Cohort were identified through pathology review. Subsequent breast cancers were identified via medical records and a questionnaire. Relative risks (RRs) were estimated using standardized incidence ratios, comparing the observed number of breast cancers with those expected based on Iowa Surveillance, Epidemiology, and End Results (SEER) data. Age, histologic factors, and family history were evaluated as risk modifiers. Plots of cumulative breast cancer incidence provided estimates of risk over time. With mean follow-up of 13.7 years, 66 breast cancers (19.9%) occurred among 331 women with atypia. RR of breast cancer with atypia was 3.88 (95% CI, 3.00 to 4.94). Marked elevations in risk were seen with multifocal atypia (eg, three or more foci with calcifications [RR, 10.35; 95% CI, 6.13 to 16.4]). RR was higher for younger women (< 45; RR, 6.76; 95% CI, 3.24 to 12.4). Risk was similar for atypical ductal and atypical lobular hyperplasia, and family history added no significant risk. Breast cancer risk remained elevated over 20 years, and the cumulative incidence approached 35% at 30 years. Among women with atypical hyperplasia, multiple foci of atypia and the presence of histologic calcifications may indicate "very high risk" status (> 50% risk at 20 years). A positive family history does not further increase risk in women with atypia.

Giant fibroadenomatoid hyperplasia of the breast: a case report.

PubMed

Zhang, Hao; Wang, Xin-Lu; Ren, Wei-Dong; Shi, Tie-Mei

2014-01-01

Fibroadenomatoid hyperplasia of the breast (FAHB) is a rare benign breast lesion and its clinical features are similar to fibroadenoma and fibrocystic changes. FAHB has been previously termed sclerosing lobular hyperplasia, fibroadenomatosis, fibroadenomatoid change, or fibroadenomatoid mastopathy. Typically, FAHB is derived from stroma and epithelia. The pathologic characteristics of FAHB are microfocal lobulocentric proliferation of stroma accompanied by epithelial and myoepithelial components resembling similar histological changes, as found in fibroadenoma, apocrine hyperplasia, intraductal hyperplasia, and lobular hyperplasia. FAHB could be present as a localized or diffused pattern in pathology. Most cases show no well-circumscribed mass lesions and no apparent capsules; it is usually identified as an incidental finding in other benign lesions or in random sampling in cancerous breast tissues. FAHB is categorized as a benign proliferative breast disease and it has previously been reported; however, the authors believe this study may be the first case with two giant masses reported. Fiber adenoma hyperplasia is a rare cystic hyperplasia of breast pathology and its ultrasonographic manifestations are easily confused with breast cancer. Comparative MRI ultrasound analysis will help make the differential diagnosis. © 2014 S. Karger AG, Basel.

Benign phyllodes tumor with tubular adenoma-like epithelial component in FNAC: A diagnostic pitfall.

PubMed

Panda, Kishori M

2016-01-01

Benign phyllodes tumor (BPT) is a biphasic neoplasm composed of bland stromal and epithelial elements. Cytologic diagnostic criteria of BPT, though documented in the literature, diagnostic pitfalls in fine-needle aspiration cytology (FNAC) may occur due to sampling error, high cellularity, ductal hyperplasia, paucity of stromal component, and occasional dissociation of epithelial cells. Here, we describe a case of BPT diagnosed by histology in a 19-year-old female, where FNAC features were inconclusive due to paucity of stromal component, predominance of tubular adenoma-like epithelial component, and due to the presence of other overlapping features with fibroadenoma.

Collagenous spherulosis presenting as a mass of the breast.

PubMed

Jan, Yee-Jee; Li, Mu-Chun; Ho, William L

2002-10-01

Collagenous spherulosis (CS) is a rare benign lesion which typically presents as an incidental microscopic finding accompanying other breast lesions. Pathologists who are not familiar with this entity occasionally misdiagnose CS as adenoid cystic carcinoma (ACC), cribriform ductal carcinoma in situ (C-DCIS), or atypical intraductal hyperplasia (AIH), especially when it presents as a mass. It is of utmost importance to differentiate benign CS from its malignant mimics in order to avoid unnecessary treatment. We report an unusual case of CS manifested as a mass in the right breast of a 45-year-old female and discuss the problems of differential diagnosis and histogenesis.

Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

PubMed

Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

2013-07-01

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report.

PubMed

Kumar, Mayank; Pottipati, Bhaswanth; Arakeri, Surekha U; Javalgi, Anita P

2017-06-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.

Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report

PubMed Central

Pottipati, Bhaswanth; Arakeri, Surekha U.; Javalgi, Anita P.

2017-01-01

Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast. PMID:28764176

An unusual melanocytic lesion associated with eccrine duct fibroadenomatosis and syringoid features.

PubMed

Stefanato, C M; Simkin, D A; Bhawan, J

2001-04-01

The intimate association of nevomelanocytic nevi with eccrine ducts commonly seen in congenital nevi was emphasized by Mishima, who described as eccrine-centered nevi those lesions characterized by nevomelanocytic cells predominantly proliferating around and within the eccrine sweat duct walls. However, there were no changes in the overlying epidermis, dermis, or eccrine acrosyringeal or dermal duct proliferation in these lesions. We present the case of a 16-year-old boy with a 1-year-history of a 0.6-cm diameter single tan papule on the right heel, clinically thought to be a Spitz nevus. Histopathologic examination revealed a compound nevomelanocytic nevus associated with epidermal hyperplasia, thin anastomosing cords of acrosyringeal epithelium extending within the dermis, and eccrine ductal proliferation in a syringoma-like pattern associated with a dense fibrous stroma. Features that distinguish our case from eccrine-centered nevus are that the latter lacks epidermal and eccrine duct hyperplasia and a dense fibrous stroma. The location of the lesion on the heel in our case suggests the possibility that the pathologic changes observed could result from repetitive trauma.

Characterization of the Chicken Ovarian Cancer Model

DTIC Science & Technology

2004-08-01

epithelium and usually contain eosinophilic proteinaceous fluid in their lumen. They have variable amounts of interstitial fibrovascular tissue and/or...alterations in oviductal glandular epithelium from normal to neoplastic (focal or multifocal hyperplasia -4 dysplasia -- adenoma [usually polypoid] -4

Breast Cancer Risk by Extent and Type of Atypical Hyperplasia: An Update from the Nurses’ Health Studies

PubMed Central

Collins, Laura C.; Aroner, Sarah; Connolly, James L.; Colditz, Graham A.; Schnitt, Stuart J.; Tamimi, Rulla M.

2015-01-01

Background Women with atypical hyperplasia (AH) on a benign breast biopsy (BBB) are at increased risk for the development of breast cancer. However, the relationship between type and extent of AH (atypical ductal hyperplasia (ADH) vs. atypical lobular hyperplasia (ALH)) and magnitude of breast cancer risk is not well-defined. Methods We conducted a nested case-control study of benign breast disease and breast cancer risk. Women with breast cancer and a prior BBB (cases=488) were matched to women with a prior BBB but free from breast cancer (controls=1907). BBB slides were reviewed and categorized as either non-proliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Results Among women with ADH, the inter-relationship between extent of atypia and breast cancer risk was not significant (OR=3.5; 95%CI 2.2-5.6 for 1-2 foci, OR= 2.7; 95%CI 1.4-5.1 for ≥3 foci; p=0.58). Similarly, while the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR=5.2; 95%CI 2.7-10.0 for 1-2 foci; OR=8.0; 95%CI 4.5-14.2 for ≥3 foci; p=0.66). Conclusion This analysis demonstrates that the extent of ADH or ALH did not significantly contribute to breast cancer risk. The lack of a significant dose-response relationship between extent and type of atypia and breast cancer risk suggests that it would be premature to use extent of atypia to influence management decisions in women with ADH or ALH. PMID:26565738

Extent of Atypical Hyperplasia Stratifies Breast Cancer Risk in Two Independent Cohorts of Women

PubMed Central

Degnim, Amy C.; Dupont, William D.; Radisky, Derek C.; Vierkant, Robert A.; Frank, Ryan D.; Frost, Marlene H.; Winham, Stacey J.; Sanders, Melinda E.; Smith, Jeffrey R.; Page, David L.; Hoskin, Tanya L.; Vachon, Celine M.; Ghosh, Karthik; Hieken, Tina J.; Denison, Lori A.; Carter, Jodi M.; Hartmann, Lynn C.; Visscher, Daniel W.

2016-01-01

Background Women with atypical hyperplasia (AH) on breast biopsy have a substantially increased risk of breast cancer (BC). Here we report BC risk with AH extent and subtype in two separate cohorts. Methods All samples containing AH were included from two cohorts of benign breast disease, Mayo Clinic and Nashville. Histology review quantified the number of foci of atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). BC risk was stratified for number of AH foci within AH subtypes. Results The study included 708 Mayo and 466 Nashville AH subjects. In the Mayo Cohort, increasing foci of AH was associated with a significant increase in risk of BC, both for ADH (RR’s of 2.61, 5.21, and 6.36 for 1, 2, and 3+ foci, p=0.006 for linear trend) and for ALH (RR’s of 2.56, 3.50, and 6.79 for 1, 2, and 3+ foci, p=0.001 for linear trend). In the Nashville Cohort, RR’s of BC for ADH were 2.70, 5.17, and 15.06 for 1, 2, and 3+ foci respectively (p<0.001 for linear trend); for ALH, RR’s also increased but not significantly (2.61, 3.48, and 4.02, p=0.148). Combining both Mayo and Nashville samples, risk increased significantly for 1, 2, and 3+ foci: RR’s of 2.65, 5.19, and 8.94 for ADH (p<0.001), and 2.58, 3.49, and 4.97 for ALH (p=0.001). Conclusions In two independent cohort studies of benign breast disease, extent of atypia stratifies long-term breast cancer risk for ADH and ALH. PMID:27352219

Upgrade of high-risk breast lesions detected on mammography in the Breast Cancer Surveillance Consortium

PubMed Central

Menes, Tehillah S.; Rosenberg, Robert; Balch, Steven; Jaffer, Shabnam; Kerlikowske, Karla; Miglioretti, Diana L.

2013-01-01

Background Upgrade rates of high-risk breast lesions after screening mammography were examined. Study design The Breast Cancer Surveillance Consortium registry was used to identify all BI-RADS 4 assessments followed by needle biopsies with high-risk lesions. Follow-up was performed for all women. Results High-risk lesions were found in 957 needle biopsies, with excision documented in 53%. Most (N=685) were atypical ductal hyperplasia (ADH), 173 were lobular neoplasia, and 99 were papillary lesions. Upgrade to cancer varied with type of lesion (18% in ADH, 10% in lobular neoplasia and 2% in papillary). In premenopausal women with ADH, upgrade was associated with family history. Cancers associated with ADH were mostly (82%) ductal carcinoma in situ, those associated with lobular neoplasia were mostly (56%) invasive. During further 2 years of follow-up, cancer was documented in 1% of women with follow-up surgery and in 3% with no surgery. Conclusion Despite low rates of surgery, low rates of cancer were documented during follow-up. Benign papillary lesions diagnosed on BI-RADS 4 mammograms among asymptomatic women do not justify surgical excision. PMID:24112677

Biliopancreatic duct injection of ethanol as an experimental model of acute and chronic pancreatitis in rats

PubMed Central

Unal, Ethem; Atalay, Suleyman; Tolan, Huseyin Kerem; Yuksekdag, Sema; Yucel, Metin; Acar, Aylin; Basak, Fatih; Gunes, Pembegul; Bas, Gurhan

2015-01-01

In the present study, we described an easily reproducable experimental pancreatits model induced by biliopancreatic duct injection of ethyl alcohol. Seventy Wistar albino rats were divided equally into seven groups randomly: the control group (group 1), acute pancreatitis groups; induced by 20% ethanol (group 2), 48% ethanol (group 3), 80% ethanol (group 4), chronic pancreatitis groups; induced by 20% ethanol (group 5), 48% ethanol (group 6) and by 80% ethanol (group 7). Acute pancreatitis groups were sacrified on postoperative day 3, while the control group and chronic pancreatitis groups were killed on postoperative day 7. Histopathologic evaluation was done, and P < 0.05 was accepted as statistically significant. All rats in group 3 developed acute pancreatitis (100%). Inflammatory infiltration of neutrophils and mononuclear cells, interstitial edema, and focal necrotic areas were seen in the pancreatic tissues. Similarly, all rats in group 6 developed chronic pancreatitis (100%). Interstitial fibrosis, lymphotic infiltration, ductal dilatation, acinar cell atrophy, periductal hyperplasia were seen in the pancreatic tissues. Mortality was seen only in group 7. The biliopancreatic ductal injection of 48% ethanol induced acute and chronic pancreatitis has 100% success rate. PMID:25785001

Improving classification with forced labeling of other related classes: application to prediction of upstaged ductal carcinoma in situ using mammographic features

NASA Astrophysics Data System (ADS)

Hou, Rui; Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2018-02-01

Predicting whether ductal carcinoma in situ (DCIS) identified at core biopsy contains occult invasive disease is an import task since these "upstaged" cases will affect further treatment planning. Therefore, a prediction model that better classifies pure DCIS and upstaged DCIS can help avoid overtreatment and overdiagnosis. In this work, we propose to improve this classification performance with the aid of two other related classes: Atypical Ductal Hyperplasia (ADH) and Invasive Ductal Carcinoma (IDC). Our data set contains mammograms for 230 cases. Specifically, 66 of them are ADH cases; 99 of them are biopsy-proven DCIS cases, of whom 25 were found to contain invasive disease at the time of definitive surgery. The remaining 65 cases were diagnosed with IDC at core biopsy. Our hypothesis is that knowledge can be transferred from training with the easier and more readily available cases of benign but suspicious ADH versus IDC that is already apparent at initial biopsy. Thus, embedding both ADH and IDC cases to the classifier will improve the performance of distinguishing upstaged DCIS from pure DCIS. We extracted 113 mammographic features based on a radiologist's annotation of clusters.Our method then added both ADH and IDC cases during training, where ADH were "force labeled" or treated by the classifier as pure DCIS (negative) cases, and IDC were labeled as upstaged DCIS (positive) cases. A logistic regression classifier was built based on the designed training dataset to perform a prediction of whether biopsy-proven DCIS cases contain invasive cancer. The performance was assessed by repeated 5-fold CrossValidation and Receiver Operating Characteristic(ROC) curve analysis. While prediction performance with only training on DCIS dataset had an average AUC of 0.607(%95CI, 0.479-0.721). By adding both ADH and IDC cases for training, we improved the performance to 0.691(95%CI, 0.581-0.801).

Radial scars diagnosed on breast core biopsy: Frequency of atypia and carcinoma on excision and implications for management.

PubMed

Donaldson, Alana R; Sieck, Leah; Booth, Christine N; Calhoun, Benjamin C

2016-12-01

The risk of finding carcinoma in excisions following a core needle biopsy diagnosis of radial scar is not well defined and clinical management is variable. The aim of this study is to determine the frequency of high-risk lesions, ductal carcinoma in situ, and invasive carcinoma in excisions following a core biopsy diagnosis of radial scar. Dedicated breast pathologists and radiologists correlated the histologic and radiologic findings and categorized radial scars as the target lesion or an incidental finding. High-risk lesions were defined as atypical hyperplasia or classical lobular carcinoma in situ. Of the 79 radial scars identified over a 14-year period, 22 were associated with atypia or carcinoma in the core biopsy. Thirty-seven (37) of the 57 benign radial scars underwent excision with benign findings in 30 (81%), high-risk lesions in six (16%), and flat epithelial atypia in one (3%). There were no upgrades to carcinoma. One patient with a benign radial scar developed a 3-mm focus of intermediate-grade estrogen receptor-positive ductal carcinoma in situ in the same quadrant of the ipsilateral breast 72 months after excision. One patient with an incidental un-excised benign radial scar was diagnosed with ductal carcinoma in situ at a separate site of suspicious calcifications. In this series, none of the benign radial scars was upgraded to carcinoma. Radial scar was the targeted lesion in all cases with high-risk lesions on excision. Surgical excision may not be mandatory for patients with benign incidental radial scars on core biopsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Papillary neoplasia of the breast: immunohistochemically defined myoepithelial cells in the diagnosis of benign and malignant papillary breast neoplasms.

PubMed

Raju, U B; Lee, M W; Zarbo, R J; Crissman, J D

1989-11-01

The presence or absence of myoepithelial cells (ME) has been considered as an important feature in the differential diagnosis of benign and malignant papillary lesions of the breast. We evaluated the distribution of myoepithelial cells in formalin-fixed paraffin-embedded tissue sections of 25 papillomas and 18 papillary carcinomas by ABC immunoperoxidase technique with antibodies to muscle actin (HHF-35) and high molecular weight (HMW) keratin (clone 34BE12, cytokeratins 1, 5, 10, and 14; reacting preferentially with ME cells) and an antiserum to S-100 protein. Also included in the study were eight cases of micropapillary ductal carcinoma in situ (DCIS) having a few fibrovascular cores and five peripheral papillomas with accompanying ductal carcinoma in situ or atypical hyperplasia. The antibodies to muscle actin were sensitive and relatively specific for ME cells of the breast and uniformly labeled ME cells in all 25 papillomas. ME cells were absent or extremely sparse in papillary carcinomas. They were present focally in some of the fibrovascular cores of the micropapillary DCIS, and a mixed pattern was observed in peripheral papillomas with areas of carcinoma. HMW keratin was variably expressed in ME cells in most cases with positive internal controls and was present in several normal ductal and papilloma epithelial cells but not in epithelial cells of papillary carcinomas. HMW keratin, although less specific for ME cells, was a useful adjunct because of its reactivity with ME cells as well as hyperplastic epithelial cells in papillomas, which resulted in a combined positive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of underestimation of malignancy after image-guided core needle biopsy diagnosis of flat epithelial atypia or atypical ductal hyperplasia.

PubMed

Yu, Chi-Chang; Ueng, Shir-Hwa; Cheung, Yun-Chung; Shen, Shih-Che; Kuo, Wen-Lin; Tsai, Hsiu-Pei; Lo, Yung-Feng; Chen, Shin-Cheh

2015-01-01

Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are precursors of breast malignancy. Management of FEA or ADH after image-guided core needle biopsy (CNB) remains controversial. The aim of this study was to evaluate malignancy underestimation rates after FEA or ADH diagnosis using image-guided CNB and to identify clinical characteristics and imaging features associated with malignancy as well as identify cases with low underestimation rates that may be treatable by observation only. We retrospectively reviewed 2,875 consecutive image-guided CNBs recorded in an electronic data base from January 2010 to December 2011 and identified 128 (4.5%) FEA and 83 (2.9%) ADH diagnoses (211 total cases). Of these, 64 (30.3%) were echo-guided CNB procedures and 147 (69.7%) mammography-guided CNBs. Twenty patients (9.5%) were upgraded to malignancy. Multivariate analysis indicated that age (OR = 1.123, p = 0.002, increase of 1 year), mass-type lesion with calcifications (OR = 8.213, p = 0.006), and ADH in CNB specimens (OR = 8.071, p = 0.003) were independent predictors of underestimation. In univariate analysis of echo-guided CNB (n = 64), mass with calcifications had the highest underestimation rate (p < 0.001). Multivariate analysis of 147 mammography-guided CNBs revealed that age (OR = 1.122, p = 0.040, increase of 1 year) and calcification distribution were significant independent predictors of underestimation. No FEA case in which, complete calcification retrieval was recorded after CNB was upgraded to malignancy. Older age at diagnosis on image-guided CNB was a predictor of malignancy underestimation. Mass with calcifications was more likely to be associated with malignancy, and in cases presenting as calcifications only, segmental distribution or linear shapes were significantly associated with upgrading. Excision after FEA or ADH diagnosis by image-guided CNB is warranted except for FEA diagnosed using mammography-guided CNB with complete calcification retrieval. © 2015 Wiley Periodicals, Inc.

Altered AIB1 or AIB1Δ3 Expression Impacts ERα Effects on Mammary Gland Stromal and Epithelial Content

PubMed Central

Nakles, Rebecca E.; Shiffert, Maddalena Tilli; Díaz-Cruz, Edgar S.; Cabrera, M. Carla; Alotaiby, Maram; Miermont, Anne M.; Riegel, Anna T.

2011-01-01

Amplified in breast cancer 1 (AIB1) (also known as steroid receptor coactivator-3) is a nuclear receptor coactivator enhancing estrogen receptor (ER)α and progesterone receptor (PR)-dependent transcription in breast cancer. The splice variant AIB1Δ3 demonstrates increased ability to promote ERα and PR-dependent transcription. Both are implicated in breast cancer risk and antihormone resistance. Conditional transgenic mice tested the in vivo impact of AIB1Δ3 overexpression compared with AIB1 on histological features of increased breast cancer risk and growth response to estrogen and progesterone in the mammary gland. Combining expression of either AIB1 or AIB1Δ3 with ERα overexpression, we investigated in vivo cooperativity. AIB1 and AIB1Δ3 overexpression equivalently increased the prevalence of hyperplastic alveolar nodules but not ductal hyperplasia or collagen content. When AIB1 or AIB1Δ3 overexpression was combined with ERα, both stromal collagen content and ductal hyperplasia prevalence were significantly increased and adenocarcinomas appeared. Overexpression of AIB1Δ3, especially combined with overexpressed ERα, led to an abnormal response to estrogen and progesterone with significant increases in stromal collagen content and development of a multilayered mammary epithelium. AIB1Δ3 overexpression was associated with a significant increase in PR expression and PR downstream signaling genes. AIB1 overexpression produced less marked growth abnormalities and no significant change in PR expression. In summary, AIB1Δ3 overexpression was more potent than AIB1 overexpression in increasing stromal collagen content, inducing abnormal mammary epithelial growth, altering PR expression levels, and mediating the response to estrogen and progesterone. Combining ERα overexpression with either AIB1 or AIB1Δ3 overexpression augmented abnormal growth responses in both epithelial and stromal compartments. PMID:21292825

Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

PubMed

Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

2012-07-01

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

Canine prostate models in preclinical studies of minimally invasive interventions: part II, benign prostatic hyperplasia models

PubMed Central

Báez-Díaz, Claudia; Sánchez-Margallo, Francisco Miguel

2017-01-01

Canine prostate is widely used as animal model in the preclinical evaluation of emerging therapeutic interventions. Spontaneous benign prostatic hyperplasia (BPH) is common in adult intact male dogs with two distinct pathological types: glandular and complex form of prostatic hyperplasia. The complex form of prostatic hyperplasia, usually occurring in older dogs, represents an ideal model because of its unique pathologic feature, including not only glandular hyperplasia but also an increase in prostate stromal components. The limited commercial availability of adult dogs with spontaneous BPH motivates experimentally induced BPH in young dogs. Hormone-induced canine BPH model has been well established with various hormonal treatment regimens and administration approaches. The goal of this review is to provide the veterinary background in spontaneous BPH in dogs, summarize the techniques in hormonal induction of canine BPH, and highlight the pathological and clinical limitations of the canine models that may lead to distinct therapeutic responses compared to clinical trials in humans. PMID:28725598

Rates of upgrade to malignancy for 271 cases of flat epithelial atypia (FEA) diagnosed by breast core biopsy.

PubMed

Peres, Alexandre; Barranger, Emmanuel; Becette, Véronique; Boudinet, Alain; Guinebretiere, Jean-Marc; Cherel, Pascal

2012-06-01

Flat epithelial atypia (FEA) is a borderline lesion that might represent an early stage in the development of certain low-grade carcinomas in situ and invasive cancers. There are no guidelines on its management. Our objectives were to determine the upgrade to malignancy rate and identify a subpopulation of patients that might undergo just mammographic surveillance. We retrospectively reviewed the data for 271 FEA cases among 5,555 breast core biopsies obtained over a 7-year period (January 2003-2010). We collated clinical data (age, history of cancer, menopausal status), radiological data (lesion type, size, Bi-Rads category), technical data (number of biopsies, needle gauge, excision quality) and histological data and sought correlations between these factors and upgrade rate. The 271 FEA comprised 128 cases of pure FEA, 135 cases of FEA + atypical ductal hyperplasia, and 8 cases of FEA + atypical lobular hyperplasia. Overall, 184 patients underwent surgery and 46 mammographic surveillance. Surgery detected 34 cases of malignancy (23 CIS, 7 invasive cancers, and 4 mixed cases) giving a 15% upgrade rate. Quality of excision was the only factor associated with under-diagnosis. The presence of FEA at biopsy warrants surgery.

[Fibrous tissue(s): a key for lesion characterization in digestive diseases].

PubMed

Régent, D; Laurent, V; Antunes, L; Debelle, L; Cannard, L; Leclerc, Jc; Beot, S

2002-02-01

Fibrosis is one of the hallmarks of inflammatory and repair processes in pathology. Various exogenous and endogenous stimuli, including tumor development, can induce inflammatory reactions. During the post-equilibrium phase after IV injection of non specific contrast media, CT and/or MR allow the study of these inflammatory answers to tumoral or infectious processes. Delayed enhancement of collagenic fibrous tissue during the late post-equilibrium phase is an essential complementary data in the characterization of many liver lesions: cirrhosis, cholangiocarcinoma, focal nodular hyperplasia, fibrous metastasis. but also for the differential diagnosis of pancreatic diseases (groove pancreatitis vs ductal adenocarcinoma) or of gastro-intestinal diseases (gastric adenocarcinoma vs lymphoma, mechanical complication vs inflammatory bouts of ileal Crohn's disease).

Multifocal Epithelial Hyperplasia of Oral Cavity Expressing HPV 16 Gene: A Rare Entity

PubMed Central

Prabhat, M. P. V.; Raja Lakshmi, Chintamaneni; Sai Madhavi, N.; Bhavana, Sujana Mulk; Sarat, Gummadapu; Ramamohan, Kodali

2013-01-01

Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus. Usually HPV involves either cutaneous or mucosal surfaces, whereas concomitant mucocutaneous involvement is extremely rare. We report such a unique case of multifocal epithelial hyperplasia involving multiple sites of oral cavity along with skin lesions in a 65-year-old female. We also discuss the probable multifactorial etiology and variable clinical presentations of the lesions, including evidence of HPV 16 expression, as detected by polymerase chain reaction. The present report illustrates the need for careful examination and prompt diagnosis of the disease, as it might be associated with high risk genotypes such as HPV 16 and 18. PMID:24455323

Imprint cytology on microcalcifications excised by vacuum-assisted breast biopsy: a rapid preliminary diagnosis.

PubMed

Fotou, Maria; Oikonomou, Vassiliki; Zagouri, Flora; Sergentanis, Theodoros N; Nonni, Afroditi; Athanassiadou, Pauline; Drouveli, Theodora; Atsouris, Efstratios; Kotzia, Evagelia; Zografos, George C

2007-04-03

To evaluate imprint cytology in the context of specimens with microcalcifications derived from Vacuum-Assisted Breast Biopsy (VABB). A total of 93 women with microcalcifications BI-RADS 3 and 4 underwent VABB and imprint samples were examined. VABB was performed on Fischer's table using 11-gauge Mammotome vacuum probes. A mammogram of the cores after the procedure confirmed the excision of microcalcifications. For the application of imprint cytology, the cores with microcalcifications confirmed by mammogram were gently rolled against glass microscope slides and thus imprint smears were made. For rapid preliminary diagnosis Diff-Quick stain, modified Papanicolaou stain and May Grunwald Giemsa were used. Afterwards, the core was dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine histological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated. According to the pathological examination, 73 lesions were benign, 15 lesions were carcinomas (12 ductal carcinomas in situ, 3 invasive ductal carcinomas), and 5 lesions were precursor: 3 cases of atypical ductal hyperplasia (ADH) and 2 cases of lobular neoplasia (LN). The observed sensitivity and specificity of the cytological imprints for cancer were 100% (one-sided, 97.5% CI: 78.2%-100%). Only one case of ADH could be detected by imprint cytology. Neither of the two LN cases was detected by the imprints. The imprints were uninformative in 11 out of 93 cases (11.8%). There was no uninformative case among women with malignancy. Imprint cytology provides a rapid, accurate preliminary diagnosis in a few minutes. This method might contribute to the diagnosis of early breast cancer and possibly attenuates patients' anxiety.

Is routine pathological evaluation of tissue from gynecomastia necessary? A 15-year retrospective pathological and literature review.

PubMed

Senger, Jenna-Lynn; Chandran, Geethan; Kanthan, Rani

2014-01-01

To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia. The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words "gynecomastia", "gynaecomastia", "gynecomazia" and "gynaecomazia". A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken. The 15-year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case). In the context of evidence-based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination.

Harnessing 3D models of mammary epithelial morphogenesis. An off the beaten path approach to identify candidate biomarkers of early stage breast cancer

PubMed Central

Rossetti, Stefano; Bshara, Wiam; Reiners, Johanna A.; Corlazzoli, Francesca; Miller, Austin; Sacchi, Nicoletta

2016-01-01

Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease. To test if critical core morphogenetic mechanisms are compromised by different mutations, we performed proteomics analysis of five mammary epithelial HME1 mutant lines that develop a DCIS-like morphology in three dimensional (3D) culture. Here we show first, that all HME1 mutant lines share a common protein signature highlighting an inverse deregulation of two annexins, ANXA2 and ANXA8. Either ANXA2 downregulation or ANXA8 upregulation in the HME1 cell context are per se sufficient to confer a 3D DCIS-like morphology. Seemingly, different mutations impinged on a common mechanism that differentially regulates the two annexins. Second, we show that ANXA8 expression is significantly higher in DCIS tissue samples versus normal breast tissue and atypical ductal hyperplasia (ADH). Apparently, ANXA8 expression is significantly more upregulated in ER- negative versus ER-positive cases, and significantly correlates with tumor stage, grade and positive lymph node. Based on our study, 3D mammary morphogenesis models can be an alternate/complementary strategy for unraveling new DCIS mechanisms and biomarkers. PMID:27422542

[Practical problems in breast screening. Columnar cell lesions including flat epithelial atypia and lobular neoplasia].

PubMed

Nährig, J

2008-11-01

Columnar cell lesions (CCL) and lobular neoplasia (LN) are encountered with increasing frequency in breast screening biopsies. CCLs are frequently associated with microcalcifications, whereas LN is an incidental finding in most cases. Flat epithelia atypia (FEA) the atypical variant of CLL, LN and atypical ductal hyperplasia (ADH) are frequently associated lesions. Molecular genetic studies of CCL, ductal carcinoma in situ (DCIS) and low grade invasive carcinomas revealed similar chromosomal alterations supporting the assumption that CCLs are neoplastic proliferations. The frequent association of FEA together with well differentiated invasive carcinomas provides further evidence of this concept. There is no internationally accepted classification of CCLs at present. CDH1-gene mutations are the cardinal feature of LN and invasive lobular carcinoma. In immunohistochemically CDH1-positive cases, alternative genetic alterations of the CDH1 pathway can lead to functional loss of CDH1. In our opinion morphologically and immunohistochemically hybrid lesions may represent this group of lobular lesions. Recent follow-up data suggest a higher rate of ipsilateral carcinomas in patients with previously diagnosed LN. It is currently an open question whether FEA and LN are members of a common family of intralobular proliferations, which are non-obligatory precursors of a low nuclear grade breast neoplasia family.

Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma.

PubMed Central

Gamallo, C.; Palacios, J.; Suarez, A.; Pizarro, A.; Navarro, P.; Quintanilla, M.; Cano, A.

1993-01-01

Recently, a correlation has been suggested between a loss of E-cadherin (E-CD) and increased invasiveness of neoplastic cells. In this study, E-CD expression in breast cancer was investigated using an affinity-purified antibody (ECCD-2) in an immunoenzymatic (avidin-biotin-alkaline phosphatase) test. Intensity and extension of E-CD immunoreactivity were evaluated in 61 breast carcinomas and correlated with their histological type and grade, nodal involvement, and hormonal receptor status. Histological types were infiltrating ductal carcinoma of no special type (n = 54) and infiltrating lobular carcinoma (n = 7). All infiltrating ductal carcinomas of no special type except two grade 3 carcinomas showed positive immunoreactivity that was variable among different cases. Grade 1 breast carcinomas (n = 10) showed greater immunoreactivity than grade 2 (n = 25) and grade 3 (n = 19) carcinomas. E-CD immunoreactivity correlated positively with the degree of tubular formation and inversely with the mitoses number. None of the infiltrating lobular carcinomas expressed E-CD in their infiltrating cells, whereas they showed only weak immunostains in areas of atypical lobular hyperplasia and lobular carcinoma in situ. These results indicate that E-CD expression correlates with histological type and grade in breast carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:7682767

Evolving concepts in the management of lobular neoplasia.

PubMed

Anderson, Benjamin O; Calhoun, Kristine E; Rosen, Eric L

2006-05-01

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.

Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies.

PubMed

Collins, Laura C; Aroner, Sarah A; Connolly, James L; Colditz, Graham A; Schnitt, Stuart J; Tamimi, Rulla M

2016-02-15

Women with atypical hyperplasia (AH) on a benign breast biopsy specimen are at increased risk for the development of breast cancer. However, the relation between the type and extent of AH (atypical ductal hyperplasia [ADH] vs atypical lobular hyperplasia [ALH]) and the magnitude of the breast cancer risk is not well defined. A nested case-control study of benign breast disease and breast cancer risk was conducted. Women with breast cancer and prior benign breast biopsy findings (488 cases) were matched to women with prior benign breast biopsy findings who were free from breast cancer (1907 controls). Benign breast biopsy slides were reviewed and categorized as nonproliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Among women with ADH, the interrelation between the extent of atypia and breast cancer risk was not significant (odds ratio [OR] for 1 or 2 foci, 3.5; 95% confidence interval [CI], 2.2-5.6; OR for ≥3 foci, 2.7; 95% CI, 1.4-5.1; P = .41). Similarly, although the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR for 1 or 2 foci, 5.2; 95% CI, 2.7-10.0; OR for ≥3 foci, 8.0; 95% CI, 4.5-14.2; P = .19). This analysis demonstrates that the extent of ADH or ALH does not significantly contribute to breast cancer risk. The lack of a significant dose-response relation between the extent and type of atypia and breast cancer risk suggests that it would be premature to use the extent of atypia to influence management decisions for women with ADH or ALH. © 2015 American Cancer Society.

Proximal location of mouse prostate epithelial stem cells

PubMed Central

Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E. Lynette

2002-01-01

Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation. PMID:12082083

Breast lymphoma occurring after an invasive ductal breast carcinoma developed in the same area: A case report and literature review.

PubMed

Demoor-Goldschmidt, C; Mahé, M-A; Supiot, S

2018-04-01

Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

A case of hirsutism due to bilateral diffuse ovarian Leydig cell hyperplasia in a post-menopausal woman.

PubMed

Ali, F S.M.; Stanaway, S E.R.S.; Zakhour, H D.; Spearing, G; Bowen-Jones, D

2003-11-01

Hyperandrogenism in females usually results from ovarian or adrenal pathology. We present a case of virilizaton due to very rare bilateral ovarian diffuse interstitial proliferation of Leydig cells with no tumour or hilar cell hyperplasia identified. Interestingly, the case was further complicated by the finding of high levels of testosterone in one adrenal vein on selective venous sampling (SVS), resulting in an unnecessary unilateral adrenalectomy. Further sampling found high levels also in the ovarian veins, and the condition was finally cured by bilateral oophorectomy.

Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.

PubMed

Holloway, Ryan W; Bogachev, Oleg; Bharadwaj, Alamelu G; McCluskey, Greg D; Majdalawieh, Amin F; Zhang, Lei; Ro, Hyo-Sung

2012-11-09

Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT)) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1(TG) mammary macrophages and epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG) macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1(TG) macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis.

Stromal Adipocyte Enhancer-binding Protein (AEBP1) Promotes Mammary Epithelial Cell Hyperplasia via Proinflammatory and Hedgehog Signaling*

PubMed Central

Holloway, Ryan W.; Bogachev, Oleg; Bharadwaj, Alamelu G.; McCluskey, Greg D.; Majdalawieh, Amin F.; Zhang, Lei; Ro, Hyo-Sung

2012-01-01

Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1TG) mice, and the onset of ductal hyperplasia was accelerated in AEBP1TG mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1TG bone marrow cells into non-transgenic (AEBP1NT) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1TG mammary macrophages and epithelium. Shh expression was induced in AEBP1TG macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1TG mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1TG peritoneal macrophages. The conditioned AEBP1TG macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1TG macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis. PMID:22995915

Gastrointestinal metastases from breast cancer: report of two cases.

PubMed

Gerova, Vanya A; Tankova, Ludmila T; Mihova, Anna A; Drandarska, Ivanka L; Kadian, Hilda O

2012-01-01

Metastatic involvement of the gastrointestinal (GI) tract secondary to breast cancer (BC) is rare and usually occurs in patients with lobular BC. We report 2 cases with GI presentations of metastatic BC. In the first case endoscopy and endoscopic ultrasonography because of abdominal discomfort, tenesmus and rectal bleeding demonstrated liver, gastric and rectal metastases with histological and immunohistological patterns of metastatic lobular BC. In the second case gastric involvement, endoscopically presented as a solid nodular lesion in the gastric body and fundus with involvement of the gastro-esophageal junction, was established with clinical symptoms of solid food dysphagia and dyspepsia; the metastatic infiltration from ductal BC was proven histologically and immunohistochemically. The GI metastases were presented 5 and 7 years after radical mastectomy because of lobular and ductal BC respectively. The cases are of interest with a feature of liver and GI metastases in double sites (stomach and rectum) from lobular BC, as well as solid gastric metastasis from ductal BC. They illustrate the need for special attention to GI metastatic disease in patients with invasive BC who present with non-specific GI symptoms.

Obstructive Jaundice as an Uncommon Manifestation of Metastatic Breast Cancer.

PubMed

Budimir, Ivan; Sabol Pusic, Mateja; Nikolic, Marko; Dorosulic, Zdravko; Ljubicic, Neven; Stajduhar, Emil; Mise, Ivana; Vazdar, Ljubica; Sarcevic, Bozena

2015-02-01

Invasive ductal carcinoma is the most common type of breast cancer and accounts for about 70-85% of all invasive breast carcinomas. It primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain. Most of breast cancer recurrence occurs within the first 5 years of diagnosis, particularly for ER negative disease. Gastrointestinal tract involvement is very rare and is detected in only 10% of all the cases, and it usually derives from lobular breast cancer rather than the much more common cell type of ductal breast cancer. Early diagnosis is very important because it enables prompt and adequate choice of treatment and improves patient's long-term prognosis. In this report we describe an unusual case of obstructive jaundice caused by metastases from invasive ductal breast cancer to the lymph nodes of the hepatoduodenal ligament with extramural compression of the distal common bile duct and tumor invasion to the lumen of the duct. Our goal is to emphasize possible diagnostic pitfalls and increase the clinical awareness and the importance of intensive follow-up in patients with breast cancer, even years after the initial diagnosis.

Persistent Salmonellosis Causes Pancreatitis in a Murine Model of Infection

PubMed Central

Hall, Jason C.; Thotakura, Gangadaar; Crawford, Howard C.; van der Velden, Adrianus W. M.

2014-01-01

Pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma, is a serious, widespread medical condition usually caused by alcohol abuse or gallstone-mediated ductal obstruction. However, many cases of pancreatitis are of an unknown etiology. Pancreatitis has been linked to bacterial infection, but causality has yet to be established. Here, we found that persistent infection of mice with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) was sufficient to induce pancreatitis reminiscent of the human disease. Specifically, we found that pancreatitis induced by persistent S. Typhimurium infection was characterized by a loss of pancreatic acinar cells, acinar-to-ductal metaplasia, fibrosis and accumulation of inflammatory cells, including CD11b+ F4/80+, CD11b+ Ly6Cint Ly6G+ and CD11b+ Ly6Chi Ly6G− cells. Furthermore, we found that S. Typhimurium colonized and persisted in the pancreas, associated with pancreatic acinar cells in vivo, and could invade cultured pancreatic acinar cells in vitro. Thus, persistent infection of mice with S. Typhimurium may serve as a useful model for the study of pancreatitis as it relates to bacterial infection. Increased knowledge of how pathogenic bacteria can cause pancreatitis will provide a more integrated picture of the etiology of the disease and could lead to the development of new therapeutic approaches for treatment and prevention of pancreatitis and pancreatic ductal adenocarcinoma. PMID:24717768

Comparison of histologic diagnosis between stereotactic core needle biopsy and open surgical biopsy.

PubMed

Bauer, R L; Sung, J; Eckhert, K H; Koul, A; Castillo, N B; Nemoto, T

1997-06-01

This study correlates the histologic findings of stereotactic core needle biopsy (SCNB) with open surgical biopsy (OSB) and identifies which lesions can be treated definitively based only on the SCNB histology. Women who underwent SCNB between July 1, 1993, and January 1, 1969, were identified by retrospective chart review. Mammographic (MGM) lesions found by SCNB to be ductal or lobular hyperplasia with atypia, or carcinoma underwent OSB. When the histologic findings by SCNB were inconsistent with the MGM findings, the lesion also underwent OSB. 799 women underwent SCNB with 96 (12%) of these going on to OSB. MGM findings in the 92 who presented without a palpable mass included microcalcifications (MCS) in 39, mass in 47, MCS and mass in 7, and tissue distortion in 3. One hundred one breast lesions biopsied first by SCNB, then by OSB were correlated histologically. Sensitivity of SCNB is 89%, with a specificity of 94%. Eight-four women (88%) were able to have definitive treatment at time of OSB because of prior SCNB, and 703/799 (88%) of women were spared OSB entirely. SCNB accurately identifies benign breast histology and invasive cancers in women with MGM abnormalities, a distinct advantage over fine needle aspiration cytology. SCNB does not reliably identify women with DCIS and invasion. All women with SCNB diagnosis of ductal or lobular atypia should also undergo OSB.

Flat epithelial atypia on breast needle core biopsy: a retrospective study with clinical-pathological correlation.

PubMed

Lee, Tsu-Yee Joseph; Macintosh, Rebecca F; Rayson, Daniel; Barnes, Penny J

2010-01-01

There are limited data to guide clinical management when flat epithelial atypia (FEA) is identified in breast needle core biopsies (NCBs). Our objectives were to determine the frequency of malignancy in subsequent breast excisions following NCB diagnosis of FEA, and to characterize the pathological and clinical features of associated tumors. Two hundred and fifty-six breast NCBs from a retrospective search (January 1999-July 2007) were blindly reviewed for FEA/other columnar cell lesions (CCLs). NCBs with co-existing carcinoma were excluded. The study included 211 NCBs: 116 (55%) with CCLs without atypia; 40 (19%) with CCLs with atypical ductal hyperplasia (ADH), 15 (7%) with FEA and 40 (19%) with FEA and ADH; 94 cases had follow-up excisions. Ductal carcinoma in situ and/or invasive carcinoma were present in: 4/26 (15%) excisions with CCLs on NCB, 11/30 (37%) with CCLs + ADH, 1/7 (14%) with FEA alone, and 9/31 (29%) with FEA + ADH. (a) FEA was more frequently seen with ADH, than without ADH in NCBs, (b) FEA and CCLs were more frequently associated with malignancy when with ADH, and (c) tumors excised following NCB diagnosis of FEA+/-ADH had favorable prognostic factors. A conservative excision is warranted following a NCB diagnosis of FEA and ADH, and may be warranted for FEA alone.

Subcutaneous lymphoid follicular hyperplasia secondary to vaccination: correlation of ultrasound findings with clinical and histological findings.

PubMed

Castro Copete, M C; Crespo Martínez, C; Martínez García, C; Calbo Maiques, J

In recent years, the use of vaccines has been standardized within vaccination programs. Adverse effects at the puncture site are usually mild and transient. Nevertheless, in some cases, persistence subcutaneous nodules can develop; these are often underdiagnosed because they are so rare and because of the long time that can transpire between the vaccination and their appearance. Histologically, they consist of a lymphoid follicular hyperplasia that occurs as a reaction to the aluminum particles usually used as an adjuvant in some vaccines. We were unable to find any reference in the radiological literature to these soft-tissue nodules secondary to vaccination. We report the characteristic ultrasound findings that will enable radiologists to identify or strongly suspect these lesions and thereby avoid unnecessary imaging tests that might lead to confusion and inadequate management of these patients. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae.

PubMed

von Laffert, M; Stadie, V; Wohlrab, J; Marsch, W C

2011-02-01

Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia of the interfollicular epidermis with subepidermal inflammatory infiltrate might be interpreted as an inflammation-driven process basically identical to that which is evident at the terminal follicle. However, it does not lead to harmful and progressive sequelae like those (rupture, sinus tracts) seen at the terminal follicles. © 2010 The Authors. BJD © 2010 British Association of Dermatologists.

Is routine pathological evaluation of tissue from gynecomastia necessary? A 15-year retrospective pathological and literature review

PubMed Central

Senger, Jenna-Lynn; Chandran, Geethan; Kanthan, Rani

2014-01-01

OBJECTIVE: To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia. METHOD: The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words “gynecomastia”, “gynaecomastia”, “gynecomazia” and “gynaecomazia”. A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken. RESULTS: The 15-year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients’ age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case). CONCLUSIONS: In the context of evidence-based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination. PMID:25114624

Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions.

PubMed

Terris, Benoît; Dubois, Sylvie; Buisine, Marie-Pierre; Sauvanet, Alain; Ruszniewski, Philippe; Aubert, Jean-Pierre; Porchet, Nicole; Couvelard, Anne; Degott, Claude; Fléjou, Jean-Francois

2002-08-01

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas. Copyright 2002 John Wiley & Sons, Ltd.

Mammary fibroadenomatous hyperplasia in a male cat.

PubMed

Mayayo, Saray Lorna; Bo, Stefano; Pisu, Maria Carmela

2018-01-01

Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat's medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat's clinical signs. Inhibitor therapy was successful.

Atypia on breast core needle biopsies: reproducibility and significance.

PubMed

Darvishian, Farbod; Singh, Baljit; Simsir, Aylin; Ye, Weimin; Cangiarella, Joan F

2009-01-01

This study analyzes the interobserver variability in interpreting atypia on breast core needle biopsies and in each category of atypia calculates the upgrade risk of carcinoma in the subsequent surgical excision. We identified 51 cases of atypia on breast core needle biopsies performed at our institution from January 2003 to August 2006. The atypia was classified into 4 categories: atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and atypia of undetermined significance (AUS). After a tutorial session, these cases were independently reviewed by four pathologists, whose overall multi-rater kappa value for agreement on different categories of atypia was 0.79 (95% CI, 0.69-0.89), which is within the substantial agreement range. The upgrade risk in each category of atypia was as follows: ADH 20% (p = 0.04); ALH 10% (p = 0.6); FEA 16.6% (p = 0.23), and AUS 100% (p = 0.96). Based on our findings, we conclude that follow-up excision should be performed after a diagnosis of ADH. The upgrade risk did not reach statistical significance in ALH or FEA. Although follow-up excision cannot be strongly recommended in ALH and FEA, it should be considered since the upgrade risk is not negligible. Strict adherence to the diagnostic criteria and tutorial sessions can help pathologists to achieve substantial agreement in interpreting atypia on breast core needle biopsies.

Nevus sebaceus: a clinicopathological study of 168 cases and review of the literature.

PubMed

Kamyab-Hesari, Kambiz; Seirafi, Hassan; Jahan, Shahin; Aghazadeh, Nessa; Hejazi, Pardis; Azizpour, Arghavan; Goodarzi, Azadeh

2016-02-01

Nevus sebaceus is a hamartoma composed of abnormal epidermal and dermal components with clinical and histopathological features that change with aging. Prophylactic excision of the lesion was advised historically considering its potential for giving rise to malignant tumors. However, whether early prophylactic excision should be performed has been questioned recently as most of the tumors have been found to be benign in origin. The histopathologic features of 168 patients with nevus sebaceus were reviewed to determine the frequency of different histologic features as well as associated neoplastic growths. Acanthosis, papillomatosis, and basal layer pigmentation were the most frequent findings. Hyperplastic changes of the sebaceous glands became obvious during the second decade and were present in 60% of the specimens from individuals older than 20. Inflammatory infiltrate was almost invariably present. Skin adnexal changes were frequently noted, including sebaceous gland hyperplasia (93.5%) and primitive hair follicles (76.8%). In 88.5% of scalp lesions, markedly decreased terminal hair was observed. Ectopic apocrine glands were present in 55.4% of specimens, while 24.4% showed anomalous ductal sweat gland structures resembling eccrine hyperplasia. Neoplastic changes were detected in nine cases, including four trichoblastomas, three tricholemmomas, and two syringocystadenoma papilliferums. Development of malignancies in sebaceus nevi is a rare phenomenon, and decision for excision of the lesion should be made after thorough evaluation of the pros and cons. © 2015 The International Society of Dermatology.

Parasympathetic control of Na, K transport in perfused submaxillary duct of the rat.

PubMed

Schneyer, L H

1977-07-01

The effects of stimulating the parasympathetic innervation to rat submaxillary gland on ductal transport of Na, K, water, and transepithelial PD, were tested in the main excretory duct during perfusion through its lumen. During nerve stimulation, transepithelial PD was consistently decreased, usually by about 15 mV, and this decrease could be blocked by atropine but not by adrenergic blocking agents. Net flux of Na, K, or water was not significantly changed during stimulation. One-way flux of Na from the lumen also was unaffected. The decrease in PD during stimulation was not affected by substituting isethionate for Cl or increasing [K] in the luminal perfusion medium. It is concluded that parasympathetic effects are exerted on the ductal cells, but that these probably do not involve conductance changes at the luminal membrane.

Outcome of breast lesions diagnosed as lesion of uncertain malignant potential (B3) or suspicious of malignancy (B4) on needle core biopsy, including detailed review of epithelial atypia.

PubMed

Rakha, Emad A; Ho, Bernard C; Naik, Veena; Sen, Soumadri; Hamilton, Lisa J; Hodi, Zsolt; Ellis, Ian O; Lee, Andrew H S

2011-03-01

To provide updated evidence of the outcome of breast lesions of uncertain malignant potential (B3) and suspicious of malignancy (B4) diagnosed on needle core biopsy (NCB) and analyse the outcome of the different types of intraductal epithelial atypia. One-hundred and forty-nine B3 and 26 B4 NCBs diagnosed over a 2-year period (2007-2008) were compared with those diagnosed over a previous 2-year period (1998-2000). The proportion of B3 diagnoses increased from 3.1% to 4.5%, and the positive predictive value (PPV) of malignancy of a B3 core decreased from 25% to 10%. Increased diagnosis of radial scar and reductions in the PPV of lobular neoplasia and of atypical intraductal proliferation may explain the reduction in the PPV of the B3 group as a whole. There were no significant changes in the proportion of B4 diagnosis (1.1% and 0.8%) or the PPV of B4 (83% and 88%). Review of cores with intraductal atypia showed a wide range of PPVs, from 100% for suspicious of ductal carcinoma in situ, to 40% for atypical ductal hyperplasia categorized as B3, and 14% for isolated flat epithelial atypia. The study has found a decrease in the PPV for a B3 diagnosis and suggests possible explanations. © 2011 Blackwell Publishing Limited.

Growth in disorders of adrenal hyperfunction.

PubMed

Magiakou, Maria Alexandra

2004-08-01

This article reviews how growth is affected in disorders of adrenal hyperfunction. Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Adrenal androgens, when in excess, lead to advanced linear growth and skeletal maturation, and prolonged hypercortisolemia leads to the suppression of growth hormone (GH) secretion and inhibition of somatomedin C and other growth factor effects on their target tissues. In virilizing adrenal tumors height is increased at diagnosis, but after surgical cure the final height is usually in the normal range. In congenital adrenal hyperplasia height is usually compromised by advanced skeletal maturation or by suppressed growth, particularly in the first years of life, due to excess glucocorticoid treatment. The final height is reduced in both clinical forms (salt wasting and simple virilizing) and sexes in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Growth impairment is also the hallmark of Cushing syndrome of whatever etiology when it occurs in children and growing adolescents, and the final height of these patients, even after surgical cure, remains compromised. This is apparently due to direct or indirect growth impairment by the hypercortisolism during the disease, followed by inadequate catch-up growth. Although it seems that GH treatment might be beneficial for improving final height both in patients with congenital adrenal hyperplasia who have poor height predictions and in patients with Cushing disease and GH deficiency, a larger number of studies is needed to confirm this suggestion.

Management of hyperparathyroidism (PHP) in MEN2 syndromes in Europe.

PubMed

Alevizaki, Maria

2013-03-14

Hyperparathyroidism occurs in 20-30% of MEN2A syndrome patients. It is usually associated with mild disease and is frequently asymptomatic, especially in younger age. There is genotype/phenotype association and PHP is usually associated with codon 634 mutations; however association with more "rare" mutations has also been reported. The pathology of the parathyroid glands includes hyperplasia, adenoma or a combination of the two. The optimal surgical management of this entity has not been defined yet.

Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia on Needle Biopsy

PubMed Central

Menes, Tehillah S; Kerlikowske, Karla; Lange, Jane; Jaffer, Shabnam; Rosenberg, Robert; Miglioretti, Diana L.

2017-01-01

Background Atypical ductal hyperplasia (ADH) is a known strong risk factor for breast cancer. Published risk estimates are based on cohorts that included women diagnosed prior to the widespread use of screening mammograms and do not differentiate between the methods used to diagnose ADH, which may be related to size of the ADH focus. These risks may overestimate the risk of women currently diagnosed with ADH. We sought to examine the risk of invasive cancer associated with ADH diagnosed on core needle biopsy versus excisional biopsy. Design Cohort study comparing ten-year cumulative risk of invasive breast cancer in women undergoing mammography with and without a diagnosis of ADH. Setting Five breast imaging registries that participate in the National Cancer Institute–funded Breast Cancer Surveillance Consortium (BCSC). Participants Women undergoing mammography in the BCSC. Exposure Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Main outcome Ten-year cumulative risk of invasive breast cancer risk. Results The sample included 955,331 women with 1,727 diagnoses of ADH. From 1996 to 2012, the proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten years following a diagnosis of ADH, the cumulative risk of invasive breast cancer was 2.6 (95% CI 2.0, 3.4) times higher than risk in women with no ADH. ADH diagnosed via excisional biopsy was associated with an adjusted HR of 3.0 (95% CI 2.0, 4.5), and via core needle biopsy, with an HR of 2.2 (95% CI 1.5, 3.4). Ten years after an ADH diagnosis, an estimated 5.7% (95% CI 4.3, 10.1) of women were diagnosed with invasive cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk (6.7 %; 95% CI 3.0, 12.8) compared to those with ADH diagnosed via core needle biopsy (5.0%; 95% CI 2.2, 8.9). Conclusions Current 10-year risks of invasive breast cancer after a diagnosis of ADH may be lower than previously reported. The risk associated with ADH is slightly lower for women diagnosed by needle core biopsy as compared to excisional biopsy. PMID:27607465

Evaluation of the Role of Vibrational Spectroscopy in the Assessment of Vulval Disease

ClinicalTrials.gov

2017-08-03

Normal Vulval Skin; Lichen Sclerosus; High Grade Dysplasia - Usual Type ('VIN 2-3'); High Grade Dysplasia - Differentiated Type ('VIN 2-3'); Squamous Cell Carcinoma; Epithelial Hyperplasia Without Atypia; Atypia Not Otherwise Specified/ Low Grade Dysplasia ('VIN 1'); Pagets Disease of the Vulva

Benign breast lesions at risk of developing cancer--a challenging problem in breast cancer screening programs: five years' experience of the Breast Cancer Screening Program in Verona (1999-2004).

PubMed

Manfrin, Erminia; Mariotto, Renata; Remo, Andrea; Reghellin, Daniela; Falsirollo, Francesca; Dalfior, Daniela; Bricolo, Paola; Piazzola, Elena; Bonetti, Franco

2009-02-01

Cytology and core-needle biopsies are not always sufficient to exclude malignancy in benign breast lesions (BBL) that are at risk of developing cancer, and open biopsy often is mandatory. In screening programs, open biopsies performed for lesions that are at risk of developing malignancy are considered benign. The authors of this report evaluated the impact of the screen-detected BBL at risk of developing cancer that were counted in the quota of benign breast open biopsies in the Breast Cancer Screening Program of Verona. Benign open biopsies were subdivided into 4 groups according to their risk of developing cancer: Histo1, normal histology; Histo2, 'pure' BBL (fibroadenoma, fibrocystic disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele-like lesion); and Histo4, BBL with a high risk of developing cancer (atypical columnar cell hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia). Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4 was observed 26.5%. BBL at risk of developing cancer may be numerous in screening programs. It is inappropriate to include BBL at risk of developing cancer in the overall benign open biopsy rate. The authors propose separating pure BBL from lesions at higher risk of developing cancer. To date, there is no evidence to support the premise that detecting high-risk proliferative lesions leads to benefits in terms of reduced mortality; however, these lesions need to be counted separately for future evaluations. (c) 2008 American Cancer Society.

Mammary fibroadenomatous hyperplasia in a male cat

PubMed Central

Mayayo, Saray Lorna; Bo, Stefano; Pisu, Maria Carmela

2018-01-01

Case summary Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat’s medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. Relevance and novel information To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat’s clinical signs. Inhibitor therapy was successful. PMID:29568542

Papillary lesions of the breast: To excise or observe?

PubMed

Khan, Sidrah; Diaz, Adrian; Archer, Kellie J; Lehman, Rebecca R; Mullins, Tiffany; Cardenosa, Gilda; Bear, Harry D

2018-05-01

Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long-term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long-term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention. © 2017 Wiley Periodicals, Inc.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

Role of metallic stents in benign esophageal stricture

NASA Astrophysics Data System (ADS)

Shim, Chan Sup

2012-10-01

Simple esophageal strictures, which are focal, straight, and large in diameter, usually require 1 - 3 dilation sessions to relieve symptoms. However, complex strictures, which are long, tortuous, or associated with a severely compromised luminal diameter, are usually more difficult to treat with conventional bougie or balloon dilation techniques, and often have high recurrence rates. Although the permanent placement of self-expandable metal stents (SEMS) has been used to manage refractory benign esophageal strictures, this procedure is associated with additional problems, such as stricture from tissue hyperplasia, stent migration, and fistula formation. Thus, several new types of stents have been developed, including temporary SEMS, self-expandable plastic stents (SEPS), and biodegradable stents. The use of these new products has produced varied results. Temporary SEMS that have been used to relieve benign esophageal conditions have caused granulation tissue at both ends of the stent because of contact between the mucosa and the exposed metal components of the stent, thus hindering stent removal. We examined the tissue response to two new types of SEMS, a flange-type and a straighttype, each coated with a silicone membrane on the outside of the metal mesh. These two SEMS were evaluated individually and compared with a conventional control stent in animal experiments. Although the newly designed stents resulted in reduced tissue hyperplasia, and were thus more easily separated from the esophageal tissue, some degree of tissue hyperplasia did occur. We suggest that newly designed DES (drug-eluting stents) may provide an alternative tool to manage refractory benign esophageal stricture.

Epithelial tissue hyperplasia induced by the RAF inhibitor PF-04880594 is attenuated by a clinically well-tolerated dose of the MEK inhibitor PD-0325901.

PubMed

Torti, Vince R; Wojciechowicz, Donald; Hu, Wenyue; John-Baptiste, Annette; Evering, Winston; Troche, Gabriel; Marroquin, Lisa D; Smeal, Tod; Yamazaki, Shinji; Palmer, Cynthia L; Burns-Naas, Leigh Ann; Bagrodia, Shubha

2012-10-01

Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that RAF inhibitors activate extracellular signal-regulated kinase (ERK) signaling, stimulate proliferation, and induce epithelial hyperplasia in preclinical models. Because these findings raise safety concerns about RAF inhibitor development, we further investigated the underlying mechanisms. We showed that the RAF inhibitor PF-04880594 induces ERK phosphorylation and RAF dimerization in those epithelial tissues that undergo hyperplasia. Hyperplasia and ERK hyperphosphorylation are prevented by treatment with the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD-0325901 at exposures that extrapolate to clinically well-tolerated doses. To facilitate mechanistic and toxicologic studies, we developed a three-dimensional cell culture model of epithelial layering that recapitulated the RAF inhibitor-induced hyperplasia and reversal by MEK inhibitor in vitro. We also showed that PF-04880594 stimulates production of the inflammatory cytokine interleukin 8 in HL-60 cells, suggesting a possible mechanism for the skin flushing observed in dogs. The complete inhibition of hyperplasia by MEK inhibitor in epithelial tissues does not seem to reduce RAF inhibitor efficacy and, in fact, allows doubling of the PF-04880594 dose without toxicity usually associated with such doses. These findings indicated that combination treatment with MEK inhibitors might greatly increase the safety and therapeutic index of RAF inhibitors for the treatment of melanoma and other cancers. ©2012 AACR.

Histologic work-up of non-palpable breast lesions classified as probably benign at initial mammography and/or ultrasound (BI-RADS category 3).

PubMed

Gruber, R; Jaromi, S; Rudas, M; Pfarl, G; Riedl, C C; Flöry, D; Graf, O; Sickles, E A; Helbich, T H

2013-03-01

To determine the accuracy of a probably benign assessment of non-palpable breast lesions (BI-RADS category 3) at mammography and/or ultrasound with immediate histological work-up. Stereotactic or ultrasound guided core needle breast biopsy (NBB) was performed to evaluate 288 lesions, which were prospectively assessed as BI-RADS category 3. Imaging findings included 195 masses, 73 calcification cases, 16 focal asymmetries, and four architectural distortion cases. After NBB, patients underwent either open surgical biopsy (OSB) (n=204) or mammographic follow-up (n=84) for at least 24 months. Histological results of NBB were compared with those of OSB. Three of the 288 lesions (1.0%) proved to be malignant at histological work-up, two of them were ductal carcinoma in situ (DCIS) and one of them was an invasive carcinoma. NBB revealed invasive carcinoma in 1/288 (0.35%) and atypical ductal hyperplasia (ADH) in 13/288 (4.5%) lesions. OSB revealed DCIS in 2/204 (1%) and invasive carcinoma in 1/204 (0.5%) lesions. The two DCIS were underestimated as ADH by NBB. The remaining 285 (99%) lesions proved to be benign at OSB or remained stable during follow-up. Confirmed by tissue diagnosis, the low likelihood of malignancy of prospectively assessed probably benign lesions is below the 2% threshold established for BI-RADS category 3. Imaging follow-up is a safe and effective alternative to immediate histological work-up for such lesions. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Development of a diagnostic test set to assess agreement in breast pathology: practical application of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS).

PubMed

Oster, Natalia V; Carney, Patricia A; Allison, Kimberly H; Weaver, Donald L; Reisch, Lisa M; Longton, Gary; Onega, Tracy; Pepe, Margaret; Geller, Berta M; Nelson, Heidi D; Ross, Tyler R; Tosteson, Aanna N A; Elmore, Joann G

2013-02-05

Diagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods. Breast tissue biopsies were selected from the National Cancer Institute-funded Breast Cancer Surveillance Consortium sites. We used a random sampling stratified according to woman's age (40-49 vs. ≥50), parenchymal breast density (low vs. high) and interpretation of the original pathologist. A 3-member panel of expert breast pathologists first independently interpreted each case using five primary diagnostic categories (non-proliferative changes, proliferative changes without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma). When the experts did not unanimously agree on a case diagnosis a modified Delphi method was used to determine the reference standard consensus diagnosis. The final test cases were stratified and randomly assigned into one of four unique test sets. We found GRRAS recommendations to be very useful in reporting diagnostic test set development and recommend inclusion of two additional criteria: 1) characterizing the study population and 2) describing the methods for reference diagnosis, when applicable.

Majority of flat epithelial atypia diagnosed on biopsy do not require surgical excision.

PubMed

Chan, Patrick Mun Yew; Chotai, Niketa; Lai, Eileen Shujuan; Sin, Pei Yi; Chen, Juliana; Lu, Sarah Qinghui; Goh, Mui Heng; Chong, Bee Kiang; Ho, Bernard Chi Shern; Tan, Ern Yu

2018-02-01

Borderline risk lesions such as flat epithelial atypia (FEA) are increasingly being diagnosed on biopsy. The need for surgery is being debated. In this study, we determined the frequency of histological upgrade following a diagnosis of FEA on biopsy and evaluated potential predictive factors. Retrospective review was done of 194 women who underwent biopsy of indeterminate lesions (total 195 lesions) that were diagnosed as FEA. The review covered a 10-year period. Cases where malignancy was also present together with FEA within the same biopsy cores were excluded. Lesions diagnosed as FEA on biopsy were mostly asymptomatic and presented as microcalcifications on mammogram. Flat epithelial atypia was the only abnormality detected in one-third of cases, was associated with a benign or another borderline lesion in another third and was associated with atypical ductal hyperplasia (ADH) in another third. Six patients (3.1%) were later found to have ductal carcinoma-in-situ (DCIS) at surgery. The presence of ADH in the biopsy was the only predictor of histological upgrade to malignancy (P = 0.04, OR 11.24, 95% CI 1.10 - 115.10), and was present in 5 of the 6 patients. Surgery was advised in the last patient because of radiology-pathology discordance. Thirty-six lesions (18.5%) were not excised and no interval progression or malignancy was found on follow up. Histological upgrade to malignancy was uncommon in lesions found on biopsy to be FEA. Non-operative management of biopsy-proven FEA can be considered in the absence of ADH and radiology-pathology discordance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Columnar cell lesions without atypia initially diagnosed on breast needle biopsies: is imaging follow-up enough?

PubMed

Seo, Mirinae; Chang, Jung Min; Kim, Won Hwa; Park, In-Ae; Lee, Su Hyun; Cho, Nariya; Moon, Woo Kyung

2013-10-01

The purpose of this study was to evaluate the underestimation rate and predictive factor of underestimation of columnar cell lesions (CCLs) without atypia diagnosed through breast core needle biopsies (CNBs). From January 2007 through December 2011, 141 CCLs without atypia, including columnar cell change and columnar cell hyperplasia, were diagnosed in 138 women by CNB. Excisional (n = 16) or imaging follow-up (n = 125) findings were available in all cases. On a per-lesion basis, the underestimation rate and predictive factor of underestimation were evaluated. Among the 16 surgically excised lesions, there were two malignancies (one ductal carcinoma in situ and one invasive ductal carcinoma) and one lobular carcinoma in situ. Overall, the pooled underestimation rate of malignancy was 1.4% (2/141). With regard to lesion variables, the mean lesion size was significantly larger in the underestimation group of CCLs (p = 0.007). Fine pleomorphic morphology of microcalcifications (p < 0.001), the distribution of the microcalcifications (p = 0.007), BI-RADS final assessment (p = 0.001), and imaging-pathologic correlation (p < 0.001) were significantly associated with underestimation. Multivariate analysis showed that fine pleomorphic morphology of microcalcifications (p < 0.0001) was an independent predictor of underestimation in 58 lesions with microcalcifications on mammography. The overall underestimation rate of malignancy was 1.4%. Imaging follow-up is reasonable for CCLs without atypia at CNB, especially in small lesions with less suspicious imaging findings. Fine pleomorphic microcalcifications and higher BI-RADS category might be helpful in the prediction of underestimation of a high-risk lesion or malignancy.

Ultrasound-guided cable-free 13-gauge vacuum-assisted biopsy of non-mass breast lesions

PubMed Central

Seo, Jiwoon; Jang, Mijung; Yun, Bo La; Lee, Soo Hyun; Kim, Eun-Kyu; Kang, Eunyoung; Park, So Yeon; Moon, Woo Kyung; Choi, Hye Young; Kim, Bohyoung

2017-01-01

Purpose To compare the outcomes of ultrasound-guided core biopsy for non-mass breast lesions by the novel 13-gauge cable-free vacuum-assisted biopsy (VAB) and by the conventional 14-gauge semi-automated core needle biopsy (CCNB). Materials and methods Our institutional review board approved this prospective study, and all patients provided written informed consent. Among 1840 ultrasound-guided percutaneous biopsies performed from August 2013 to December 2014, 145 non-mass breast lesions with suspicious microcalcifications on mammography or corresponding magnetic resonance imaging finding were subjected to 13-gauge VAB or 14-gauge CCNB. We evaluated the technical success rates, average specimen numbers, and tissue sampling time. We also compared the results of percutaneous biopsy and final surgical pathologic diagnosis to analyze the rates of diagnostic upgrade or downgrade. Results Ultrasound-guided VAB successfully targeted and sampled all lesions, whereas CCNB failed to demonstrate calcification in four (10.3%) breast lesions with microcalcification on specimen mammography. The mean sampling time were 238.6 and 170.6 seconds for VAB and CCNB, respectively. No major complications were observed with either method. Ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) lesions were more frequently upgraded after CCNB (8/23 and 3/5, respectively) than after VAB (2/26 and 0/4, respectively P = 0.028). Conclusion Non-mass breast lesions were successfully and accurately biopsied using cable-free VAB. The underestimation rate of ultrasound-detected non-mass lesion was significantly lower with VAB than with CCNB. Trial registration CRiS KCT0002267. PMID:28628656

Assessment of Breast Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for Mammographic Breast Microcalcifications Without Mass: A STARD-Compliant Diagnostic Accuracy Article.

PubMed

Cheung, Yun-Chung; Juan, Yu-Hsiang; Ueng, Shir-Hwa; Lo, Yung-Feng; Huang, Pei-Chin; Lin, Yu-Ching; Chen, Shin-Cheh

2015-10-01

Presence of microcalcifications within the specimens frequently signifies a successful attempt of stereotactic vacuum-assisted breast biopsy (VABB) in obtaining a pathologic diagnosis of the breast microcalcifications. In this study, the authors aimed to assess and compare the accuracy and consistency of calcified or noncalcified specimens obtained from same sites of sampling on isolated microcalcifications without mass in diagnosing high-risk and malignant lesions. To the best of our knowledge, an individual case-based prospective comparison has not been reported.With the approval from institutional review board of our hospital (Chang Gung Memorial Hospital), the authors retrospectively reviewed all clinical cases of stereotactic VABBs on isolated breast microcalcifications without mass from our database. The authors included those having either surgery performed or had clinical follow-up of at least 3 years for analysis. All the obtained specimens with or without calcification were identified using specimen radiographs and separately submitted for pathologic evaluation. The concordance of diagnosis was assessed for both atypia and malignant lesions.A total of 390 stereotactic VABB procedures (1206 calcified and 1456 noncalcified specimens) were collected and reviewed. The consistent rates between calcified and noncalcified specimens were low for atypia and malignant microcalcifications (44.44% in flat epithelial atypia, 46.51% in atypical ductal hyperplasia, 55.73% in ductal carcinoma in situ, and 71.42% in invasive ductal carcinoma). The discordance in VABB diagnoses indicated that 41.33% of malignant lesions would be misdiagnosed by noncalcified specimens. Furthermore, calcified specimens showed higher diagnostic accuracy of breast cancer as compared with the noncalcified specimens (91.54 % versus 69.49%, respectively). The evaluation of both noncalcified specimens and calcified specimens did not show improvement of diagnostic accuracy as compared with evaluating calcified specimens alone (91.54% versus 91.54%, respectively).The high prevalence of diagnostic discordance between the calcified and noncalcified specimens indicated the higher value of calcified specimens in diagnosing atypia and malignant microcalcifications. Noncalcified specimens did not provide additional diagnostic benefit from this study. The separation of calcified and noncalcified specimens may facilitate more focused interpretation from pathologists among the large number of specimens.

Is excision biopsy of fibroadenomas based solely on size criteria warranted?

PubMed

Neville, Grace; Neill, Cathleen O'; Murphy, Rosemary; Corrigan, Mark; Redmond, Paul H; Feeley, Linda; Bennett, Michael W; O'Connell, Fionnuala; Browne, Tara Jane

2018-05-25

Fibroadenomas (FA) are the most common benign tumor in the female breast. Most are managed conservatively provided there is clinical, radiologic, and pathologic concordance. However, surgical excision is typically recommended for cellular fibroepithelial lesions or those lesions with clinical, radiologic, or pathologic features concerning for phyllodes tumor (PT). Some studies have suggested surgical excision in all FA >30 mm to reduce core needle biopsy (CNB) sampling errors. The aim of our study was to evaluate, in the absence of any other concerning clinicopathologic features, whether surgical excision of FA was warranted based on size criteria alone. Cork University Hospital is a large academic center in Southern Ireland. Its breast cancer center provides both a screening and symptomatic service and diagnoses approximately 600 cancers per year. The breast histopathological data base was reviewed for all CNBs from January 1, 2010, to June 30, 2015, with a diagnosis of FA that went on to have excision at our institution. We excluded all cellular fibroepithelial lesions and those cases with co-existent lobular neoplasia, ductal carcinoma in situ, invasive carcinoma, atypical ductal hyperplasia, or lesions which would require excision in their own right. Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. Patient demographics and preoperative radiologic size and the radiologic target were recorded in each case. All radiology was reviewed by a breast radiologist prior to inclusion in the study, and there was histologic radiologic concordance with a diagnosis of FA in all cases. A total of 12,109 consecutive radiologically guided CNB were performed January 2010-June 2015; 3438 with a diagnosis of FA were identified of which 290 cases went on to have surgical excision. Of those 290 cases; 98.28% (n = 285) were confirmed as FA on excision. The remaining 1.72% (n = 5) had atypical features-FA with LCIS (n = 1), benign PT (n = 3), and invasive ductal carcinoma (n = 1). Our study suggests that, excision based solely on size is not warranted in clinical and radiologically concordant cases with a diagnosis of FA on CNB. © 2018 Wiley Periodicals, Inc.

Multinucleate cell angiohistiocytoma: a fibrohistiocytic proliferation with increased mast cell numbers and vascular hyperplasia.

PubMed

Puig, Lluís; Fernández-Figueras, María-Teresa; Bielsa, Isabel; Lloveras, Betlem; Alomar, Agustín

2002-04-01

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon lesion clinically characterized by multiple papules usually located on the face and acral regions of elderly women. Histopathologically, MCAH is characterized by dermal vascular hyperplasia associated with increased number of factor XIIIa-positive fibrohistiocytic cells and multinucleate cells with scalloped borders. We report the clinical, histopathological and immunohistochemical features of three cases of MCAH, with ulstrastructural study in one of them. The patients were a woman and two men of 56, 40 and 70 years of age, respectively. They all had multiple dull-red papules, which had appeared over several years and were located on the face, the trunk and the dorsa of the hands, respectively. The reticular dermis presented a fibrohistiocytic proliferation of factor XIIIa-positive cells, with abundant bizarre multinucleate cells and vascular hyperplasia. Increased mast cell numbers were seen in all cases, often in apposition to multinucleate cells. Histopathological differential diagnosis of MCAH includes mainly angiofibromas and dermatofibromas, even though vascular hyperplasia can be prominent and has led to many authors to classify MCAH among vascular tumors. Bizarre multinucleate cells can be found in reactive, neoplastic and inflammatory lesions in many sites of the body, and mast cells can play a role in their morphogenesis.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease.

PubMed

Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A

2015-11-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4-5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease

PubMed Central

Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A.

2015-01-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4–5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. PMID:26255741

Juvenile Papillomatosis (Swiss-Cheese Disease) of Breast in an Adult Male With Sequential Diagnoses of Ipsilateral Intraductal, Invasive, and Widely Metastatic Carcinoma: A Case Report and Review of the Disease in Males.

PubMed

Viswanathan, Kartik; McMillen, Brian; Cheng, Esther; D'Alfonso, Timothy; Patel, Ami; Hoda, Syed A

2017-09-01

Juvenile papillomatosis of the breast (JPB, also known as Swiss cheese disease) is a rare ailment that typically afflicts young females, and presents as a mass-forming lesion. The lesional mass usually comprises multiple cysts and duct stasis, amid a variety of proliferative and nonproliferative epithelial changes. The proliferative changes include papillary hyperplasia, florid hyperplasia, and papillary apocrine hyperplasia. Concurrent carcinoma (either in situ or invasive) is present in approximately 10% of cases at presentation, and subsequent carcinoma (either in situ or invasive) is diagnosed in about 10% of patients. About 20% of patients have a strong family history of breast carcinoma. A total of 10 cases of JPB have been previously reported in males, both children and adults, only one of which, in a 33-year-old, was associated with invasive carcinoma. Here, another case of JPB in a 45-year-old male-one with subsequent sequential diagnoses of ipsilateral intraductal carcinoma, invasive carcinoma, and widely metastatic carcinoma over the course of 15 years-is reported.

Management of splenic and pancreatic trauma.

PubMed

Girard, E; Abba, J; Cristiano, N; Siebert, M; Barbois, S; Létoublon, C; Arvieux, C

2016-08-01

The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately beneath the ribs. Injury to the more deeply placed pancreas is classically characterized by discordance between the severity of pancreatic injury and its initial clinical expression. For the patient who presents with hemorrhagic shock and ultrasound evidence of major hemoperitoneum, urgent "damage control" laparotomy is essential; if splenic injury is the cause, prompt "hemostatic" splenectomy should be performed. Direct pancreatic injury is rarely the cause of major hemorrhage unless a major neighboring vessel is injured, but if there is destruction of the pancreatic head, a two-stage pancreatoduodenectomy (PD) may be indicated. At open laparotomy when the patient's hemodynamic status can be stabilized, it may be possible to control splenic bleeding without splenectomy; it is always essential to search for injury to the pancreatic duct and/or the adjacent duodenum. Pancreatic contusion without ductal rupture is usually treated by drain placement adjacent to the injury; ductal injuries of the pancreatic body or tail are treated by resection (distal pancreatectomy with or without splenectomy), with generally benign consequences. For injuries of the pancreatic head with pancreatic duct disruption, wide drainage is usually performed because emergency PD is a complex gesture prone to poor results. Postoperatively, the placement of a ductal stent by endoscopic retrograde catheterization may be decided, while management of an isolated pancreatic fistula is often straightforward. Non-operative management is the rule for the trauma victim who is hemodynamically stable. In addition to the clinical examination and conventional laboratory tests, investigations should include an abdominothoracic CT scan with contrast injection, allowing identification of all traumatized organs and assessment of the severity of injury. In this context, non-operative management (NOM) has gradually become the standard as long as the patient remains hemodynamically stable and there is no suspicion of injury to hollow viscera, with the patient being carefully monitored on a surgical service. The development of arteriography with splenic artery embolization has increased the rate of splenic salvage; this can be performed electively based on specific indications (blush on CT, pseudoaneurysm, arteriovenous fistula), and may also be considered for severe splenic injury, abundant hemoperitoneum, or severe polytrauma. For pancreatic injury, in addition to CT scan, magnetic resonance pancreatography (MRCP) or even endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to identify a ductal rupture. If the pancreatic duct is intact, laboratory and CT imaging surveillance is performed just as for splenic injury. In case of pancreatic ductal injury, ERCP stenting can be considered. However, if this is unsuccessful, the therapeutic decision can be difficult: while NOM can still be successful, complications may arise that are difficult to treat while distal pancreatectomy, although initially more agressive may avoid these complications if performed early. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Identification of Stem Cells in a Novel Human Mammary Epithelial Culture (HMEC) System that Reproducibly Demonstrates Ductal Organotypic Architecture in 3 Weeks

DTIC Science & Technology

2006-10-01

diagnostic for the inherited cancer- prone disease xeroderma pigmentosum , where it is usually performed in lymphocytes or skin fibroblasts. Our novel HME...Waugh AP, Hawk JL: Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum , Cockayne’s...internal neoplasia: evidence from xeroderma pigmentosum . Carcinogenesis 1984, 5:511-514. 38. Forlenza MJ, Latimer JJ, Baum A: The effects of stress on

Identification of Stem Cells in a Novel Human Mammary Epithelial Culture (HMEC) System that Reproducibly Demonstrates Ductal Organotypic Architecture in 3 Weeks

DTIC Science & Technology

2005-10-01

diagnostic for the inherited cancer- prone disease xeroderma pigmentosum , where it is usually performed in lymphocytes or skin fibroblasts. Our novel HME...Waugh AP, Hawk JL: Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum , Cockayne’s...internal neoplasia: evidence from xeroderma pigmentosum . Carcinogenesis 1984, 5:511-514. 38. Forlenza MJ, Latimer JJ, Baum A: The effects of stress on

Cellular features of endometrial hyperplasia and well differentiated adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the cytoarchitecture of tissue fragments.

PubMed

Norimatsu, Yoshiaki; Shimizu, Keiko; Kobayashi, Tadao K; Moriya, Takuya; Tsukayama, Choutatsu; Miyake, Yasuyuki; Ohno, Eiji

2006-04-25

Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs). Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. The results of the current study revealed that cytoarchitectural criteria appear to be more useful for the cytologic assessment of endometrial lesions, especially for the diagnosis of endometrial hyperplasia and Grade 1 adenocarcinoma. Copyright 2006 American Cancer Society.

Diffuse idiopathic hyperplasia of the sternocleidomastoid muscle in a child

PubMed Central

Pal, Kamalesh; Bhat, Nisar; Moghazy, Khaled; Mitra, DK; Hegazi, Mohammed

2009-01-01

Unilateral diffuse or localized enlargement of the sternocleidomastoid muscle (SCM) is an event commonly seen in infancy, and is popularly known as ‘sternocleidomastoid tumor’. The condition, which usually spontaneously resolves with or without physiotherapy, is due to a hematoma following a difficult labor. The muscle regains its elasticity and complete function. In some infants it resolves with fibromatous changes in the muscle leading to shortening, fibrosis and finally culminating in torticollis. We describe a case of idiopathic diffuse enlargement of unilateral SCM in a 12-year-old child without any functional compromise or torticollis. The histopathological and clinical characteristics differentiating it from more commonly described sternocleidomastoid tumor or fibromatosis coli are described. We believe this is the first case report of idiopathic hyperplasia of SCM. PMID:19847086

A theory of the genesis of breast duct papilloma.

PubMed

WHANG, J

1960-03-01

While it is not the intent to argue that papilloma never develops in the conventionally accepted manner (proliferative growth from the wall of a pre-existing cavity) a new, perhaps alternative, genesis is suggested. The concept is that, beginning with the usual lobular structure of the breast, first by hyperplasia and then by coalescence of alveoli, seen earliest at the periphery of the lobule, spaces appear between the content of the lobule and the wall. By confluence of these spaces a larger cystic cavity is formed. Coalescence of alveoli through the body of the central mass, in the same way as at the periphery, develops the familiar pattern of "papilloma." Following the earlier hyperplasia, regressive changes appear and may go on to complete disintegration of the papillary mass, leaving a smooth-walled cavity.

A comparison of diagnostic performance of vacuum-assisted biopsy and core needle biopsy for breast microcalcification: a systematic review and meta-analysis.

PubMed

Huang, Xu Chen; Hu, Xu Hua; Wang, Xiao Ran; Zhou, Chao Xi; Wang, Fei Fei; Yang, Shan; Wang, Gui Ying

2018-03-16

Core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) are both popularly used breast percutaneous biopsies. Both of them have become reliable alternatives to open surgical biopsy (OSB) for breast microcalcification (BM). It is controversial that which biopsy method is more accurate and safer for BM. Hence, we conducted this meta-analysis to compare the diagnostic performance between CNB and VAB for BM, aiming to find out the better method. Articles according with including and excluding criteria were collected from the databases, PubMed, Embase, and the Cochrane Library. Preset outcomes were abstracted and pooled to find out the potential advantages in CNB or VAB. Seven studies were identified and entered final meta-analysis from initially found 138 studies. The rate of ductal carcinoma in situ (DCIS) underestimation was significantly lower in VAB than CNB group [risk ratio (RR) = 1.83, 95% confidence interval (CI) 1.40 to 2.40, p < 0.001]. The microcalcification retrieval rate was significantly higher in VAB than CNB group (RR = 0.89, 95% CI 0.81 to 0.98, p = 0.02), while CNB owned a significantly lower complication rate than VAB (RR = 0.18, 95% CI 0.03 to 0.93, p = 0.04). The atypical ductal hyperplasia (ADH) underestimation rates were not compared for the limited number of studies reporting this outcome. Compared with CNB, VAB shows better diagnostic performance in DCIS underestimation rate and microcalcification retrieval rate. However, CNB shows a significantly lower complication rate. More studies are needed to verify these findings.

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

PubMed Central

Acharya, Sunil; Xu, Jia; Wang, Xiao; Jain, Shalini; Wang, Hai; Zhang, Qingling; Chang, Chia-Chi; Bower, Joseph; Arun, Banu; Seewaldt, Victoria; Yu, Dihua

2016-01-01

Tamoxifen and aromatase inhibitors (AIs) have shown efficacy in prevention of estrogen receptor-positive (ER+) breast cancer; however, there exists no proven prevention strategy for estrogen receptor-negative (ER-) breast cancer. Up to 40% of ER- breast cancers have human epidermal growth factor receptor 2 overexpression (HER2+), suggesting HER2 signaling might be a good target for chemoprevention for certain ER- breast cancers. Here, we tested the feasibility of the HER2-targeting agent lapatinib in prevention and/or early intervention of an ER-/HER2+ early-stage breast disease model. We found that lapatinib treatment forestalled the progression of atypical ductal hyperplasia (ADH)-like acini to ductal carcinoma in situ (DCIS)-like acini in ER-/HER2+ human mammary epithelial cells (HMECs) in 3D culture. Mechanistically, we found that inhibition of HER2/Akt signaling by lapatinib led to downregulation of GLUT4 and a reduced glucose uptake in HER2-overexpressing cells, resulting in decreased proliferation and increased apoptosis of these cells in 3D culture. Additionally, our data suggest that HER2-driven glycolytic metabolic dysregulation in ER-/HER2+ HMECs might promote early-stage breast disease progression, which can be reversed by lapatinib treatment. Furthermore, low-dose lapatinib treatment, starting at the early stages of mammary grand transformation in the MMTV-neu* mouse model, significantly delayed mammary tumor initiation and progression, extended tumor-free survival, which corresponded to effective inhibition of HER2/Akt signaling and downregulation of GLUT4 in vivo. Taken together, our results indicate that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. PMID:27293993

Analysis of false results in a series of 835 fine needle aspirates of breast lesions.

PubMed

Willis, S L; Ramzy, I

1995-01-01

To analyze cases of false diagnoses from a large series to help increase the accuracy of fine needle aspiration of palpable breast lesions. The results of FNA of 835 palpable breast lesions were analyzed to determine the reasons for false positive, false negative and false suspicious diagnoses. Of the 835 aspirates, 174 were reported as positive, 549 as negative and 66 as suspicious or atypical but not diagnostic of malignancy. Forty-six cases were considered unsatisfactory. Tissue was available for comparison in 286 cases. The cytologic diagnoses in these cases were reported as follows: positive, 125 (43.7%); suspicious, 33 (11.5%); atypical, 18 (6.2%); negative, 92 (32%); and unsatisfactory, 18 (6.2%). There was one false positive diagnosis, yielding a false positive rate of 0.8%. This lesion was a case of fibrocystic change with hyperplasia, focal fat necrosis and reparative atypia. There were 14 false negative cases, resulting in a false negative rate of 13.2%. Nearly all these cases were sampling errors and included infiltrating ductal carcinomas (9), ductal carcinomas in situ (2), infiltrating lobular carcinomas (2) and tubular carcinoma (1). Most of the suspicious and atypical lesions proved to be carcinomas (35/50). The remainder were fibroadenomas (6), fibrocystic change (4), gynecomastia (2), adenosis (2) and granulomatous mastitis (1). A positive diagnosis of malignancy by FNA is reliable in establishing the diagnosis and planning the treatment of breast cancer. The false-positive rate is very low, with only a single case reported in 835 aspirates. Most false negatives are due to sampling and not to interpretive difficulties. The category "suspicious but not diagnostic of malignancy" serves a useful purpose in management of patients with breast lumps.

Fast MRI-guided vacuum-assisted breast biopsy: initial experience.

PubMed

Liberman, Laura; Morris, Elizabeth A; Dershaw, D David; Thornton, Cynthia M; Van Zee, Kimberly J; Tan, Lee K

2003-11-01

The purpose of this study was to evaluate a new method for performing MRI-guided vacuum-assisted breast biopsy in a study of lesions that had subsequent surgical excision. SUBJECTS AND METHODS. Twenty women scheduled for MRI-guided needle localization and surgical biopsy were prospectively entered in the study. MRI-guided biopsy was performed with a vacuum-assisted probe, followed by placement of a localizing clip, and then needle localization for surgical excision. Vacuum-assisted biopsy and surgical histology were correlated. Vacuum-assisted biopsy was successfully performed in 19 (95%) of the 20 women. The median size of 27 MRI-detected lesions that had biopsy was 1.0 cm (range, 0.4-6.4 cm). Cancer was present in eight (30%) of 27 lesions and in six (32%) of 19 women; among these eight cancers, five were infiltrating and three were ductal carcinoma in situ (DCIS). Among these 27 lesions, histology was benign at vacuum-assisted biopsy and at surgery in 19 (70%), cancer at vacuum-assisted biopsy in six (22%), atypical ductal hyperplasia at vacuum-assisted biopsy and DCIS at surgery in one (4%), and benign at vacuum-assisted biopsy with surgery showing microscopic DCIS that was occult at MRI in one (4%). The median time to perform vacuum-assisted biopsy of a single lesion was 35 min (mean, 35 min; range, 24-48 min). Placement of a localizing clip, attempted in 26 lesions, was successful in 25 (96%) of 26, and the clip was retrieved on specimen radiography in 22 (96%) of 23. One complication occurred: a hematoma that resolved with compression. MRI-guided vacuum-assisted biopsy is a fast, safe, and accurate alternative to surgical biopsy for breast lesions detected on MRI.

Elevated Expression of IRS-1 Associates with p-Akt Expression and Predicts Poor Prognosis of Breast Invasive Ductal Carcinoma.

PubMed

Luo, Jiadi; Feng, Juan; Wen, Qiuyuan; Qoyawayma, Christopher; Wang, Weiyuan; Chen, Lingjiao; Lu, Junmi; Zhan, Yuting; Xu, Lina; Zang, Hongjing; Fan, Songqing; Chu, Shuzhou

2018-03-15

Overexpression of Insulin Receptor Substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis. And phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status. The results showed that the percentage of either elevated expression of IRS-1 or positive p-Akt expression in BIDC is significantly higher than that in control breast tissue from non-cancer patients (P<.001, P=.001, respectively). Overexpression of IRS-1 was evidently associated with positive expression of p-Akt (r=.337, P<.001). Also, positive percentage of p-Akt expression was statistically different among different molecular subtypes of BIDC (highest in luminal B BIDC, P=.009). Furthermore, significantly worse overall survival was in BIDC patients with high expression of IRS-1 and p-Akt than patients with low expression (P=.006, P=.004, respectively). The multivariate Cox proportional hazard regression analysis showed that high expression of IRS-1 and positive expression of p-Akt protein were independent poor prognostic factors for patients with BIDC (P=.022, P=.046, respectively). In conclusion, we report for the first time that overexpression of IRS-1 protein associates with expression of p-Akt, and overexpression of IRS-1 and positive expression of p-Akt might be independent biomarkers for poor prognosis in BIDC. Copyright © 2018. Published by Elsevier Inc.

Should we excise? Are there any clinical or histologic features that predict upgrade in papillomas, incidental or non-incidental?

PubMed

Zaleski, Michael; Chen, Yun An; Chetlen, Alison L; Mack, Julie; Xu, Liyan; Dodge, Daleela G; Karamchandani, Dipti M

2018-05-11

The clinical decision to excise intraductal papilloma (IDP) without atypia diagnosed on biopsy remains controversial. We sought to establish clinical and histologic predictors (if any) which may predict upgrade in IDP. 296 biopsies (in 278 women) with histologic diagnosis of IDP without atypia were retrospectively identified and placed into Incidental (no corresponding imaging correlate), or Non-incidental (positive imaging correlate) groups. 253/296 (85.5%) cases were non-incidental, and 43/296 (14.5%) were incidental. 73.1% (185/253) non-incidental and 48.8% (21/43) incidental cases underwent excision. 12.4% (23/185) non-incidental cases underwent an upgrade to cancer or high-risk lesion; namely 8-Ductal carcinoma in situ (DCIS), 8-atypical ductal hyperplasia (ADH), 6-lobular neoplasia, and 1-flat epithelial atypia. There was no histopathologic feature on the biopsy in the non-incidental group which predicted upgrade; however a past history of atypia was significantly associated with upgrade. 2 of the 21 incidental cases upgraded (1 to ADH and 1 to lobular neoplasia); the former had a past history of ADH. Both incidental upgrades were >1 mm in size, and were not completely excised on the biopsy. None of the incidental cases which appeared completely excised on biopsy upgraded, irrespective of the size on biopsy. These findings suggest that all non-incidental IDPs should be considered candidates for surgical excision, given the 12.4% upgrade rate and no definitive histologic predictors of upgrade. Patients with incidental IDPs (if <1 mm, completely excised on biopsy and with no history of high risk breast lesion) can be spared excision. Copyright © 2018 Elsevier Inc. All rights reserved.

Pseudoangiomatous stromal hyperplasia with multinucleated stromal giant cells is neither exceptional in gynecomastia nor characteristic of neurofibromatosis type 1.

PubMed

Pižem, Jože; Velikonja, Mojca; Matjašič, Alenka; Jerše, Maja; Glavač, Damjan

2015-04-01

Six cases of gynecomastia with pseudoangiomatous stromal hyperplasia (PASH) and multinucleated stromal giant cells (MSGC) associated with neurofibromatosis type 1 (NF1) have been reported, and finding MSGC within PASH in gynecomastia has been suggested as being a characteristic of NF1. The frequency of PASH with MSGC in gynecomastia and its specificity for NF1 have not, however, been systematically studied. A total of 337 gynecomastia specimens from 215 patients, aged from 8 to 78 years (median, 22 years) were reevaluated for the presence of PASH with MSGC. Breast tissue samples of 25 patients were analyzed for the presence of an NF1 gene mutation using next generation sequencing. Rare MSGC, usually in the background of PASH, were noted at least unilaterally in 27 (13 %) patients; and prominent MSGC, always in the background of PASH, were noted in 8 (4 %) patients. The NF1 gene was mutated in only 1 (an 8-year-old boy with known NF1 and prominent MSGC) of the 25 tested patients, including 6 patients with prominent MSGC and 19 patients with rare MSGC. MSGC, usually in the background of PASH, are not characteristic of NF1.

Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia.

PubMed

Raff, Hershel; Sharma, Susmeeta T; Nieman, Lynnette K

2014-04-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing's syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing's syndrome). Endogenous Cushing's syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing's syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. © 2014 American Physiological Society.

Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

PubMed Central

Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

2014-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

ClinicalTrials.gov

2011-12-07

Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

Pathology of excessive production of growth hormone.

PubMed

Scheithauer, B W; Kovacs, K; Randall, R V; Horvath, E; Laws, E R

1986-08-01

Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of growth hormone adenomas. Resection of these GHRH-producing neoplasms results in reversal of endocrinological and sellar abnormalities. Future efforts should be directed toward the elucidation of the aetiology of pituitary adenomas, specifically whether they represent a proliferative process having its origin in endocrinological imbalance, presumably a hypothalamic abnormality, or whether it has a 'de novo' origin in the 'usual process of neoplastic transformation'.

Clinical aspects of ECL-cell abnormalities.

PubMed Central

Hirschowitz, B. I.

1998-01-01

ECL cell hyperplasia results from hypergastrinemia, and in man this occurs due to achlorhydria in atrophic gastritis (pernicious anemia [PA]) and gastrinoma (Zollinger-Ellison syndrome [ZES]). Progression to neoplasia, i.e., ECL cell carcinoids (usually small, multicentric and non-functional), occurs in some five to 10 percent of patients with PA where they remain gastrin-dependent and reversible by normalization of serum gastrin by antrectomy. Even if untreated, the carcinoids are almost invariably benign and do not cause death. In ZES, ECL cell hyperplasia is progressive due to hypergastrinemia. However, carcinoids develop only in the MEN-I subtype but pose no additional threat of malignancy. A conservative approach is recommended for small multicentric carcinoids, and the tumors do not need removal. By contrast, single, large, non-gastrin-dependent carcinoids represent a different biological and clinical problem and are frequently malignant. PMID:10461361

Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells.

PubMed

Al-Adsani, Amani; Burke, Zoë D; Eberhard, Daniel; Lawrence, Katherine L; Shen, Chia-Ning; Rustgi, Anil K; Sakaue, Hiroshi; Farrant, J Mark; Tosh, David

2010-10-27

The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes. AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBPβ (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBPβ in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBPβ, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype. These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBPβ.

Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

PubMed

Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

2013-02-01

This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P < 0.001). We observed positive significant correlations between stromal myofibroblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myofibroblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P < 0.001).  MVC was inversely related to stromal myofibroblasts in invasive cancer (P < 0.001) and DCIS (P < 0.001), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001).  Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts in stroma of tumor; probably may be a worse prognostic factor  and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression.

Inflammatory papillary hyperplasia: A systematic review

PubMed Central

Gual-Vaqués, Patricia; Jané-Salas, Enric; Egido-Moreno, Sonia; Ayuso-Montero, Raúl; Marí-Roig, Antoni

2017-01-01

Introduction Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa. It is usually found in denture-wearers but also has been reported in patients without a history of use of a maxillary prosthesis use. Objetives The aim of this study is to review the literature to assess the prevalence of denture stomatitis and inflammatory papillary hyperplasia and the etiological factors associated. Material and Methods A search was carried out in PubMed (January 2005 to October 2015) with the key words “inflammatory papillary hyperplasia”, “denture stomatitis”, “granular stomatitis” and “Newton’s type III” The inclusion criteria were studies including at least a sample of 50 apparently healthy patients, articles published from 2005 to 2015 written in English. The exclusion criteria were reviews and non-human studies. Results Out of the 190 studies obtained initially from the search 16 articles were selected to be included in our systematic review. The prevalence of denture stomatitis was 29.56% and 4.44% for IPH. We found 5 cases of denture stomatitis among non-denture-wearer individuals. All IPH cases were associated with the use of prosthesis. Smoking and continued use of ill-fitting dentures turned out to be the most frequent risk factors for developing IPH. Conclusions IPH is a rare oral lesion and its pathogenesis still remains unclear. Its presentation among non-denture-wearers is extremely unusual. Key words:Inflammatory papillary hyperplasia, denture stomatitis, prevalence, granular stomatitis, Newton’s type III stomatitis. PMID:27918740

Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model.

PubMed

Linsk, Ali; Mehta, Tejas S; Dialani, Vandana; Brook, Alexander; Chadashvili, Tamuna; Houlihan, Mary Jane; Sharma, Ranjna

2018-03-01

Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are commonly seen on breast core needle biopsy (CNB). Many institutions recommend excision of these lesions to exclude malignancy. A retrospective chart review was performed on patients who had ADH, ALH, or LCIS on breast CNB from 1/1/08 to 12/31/10 who subsequently had surgical excision of the biopsy site. Study objectives included determining upgrade to malignancy at surgical excision, identification of predictors of upgrade, and validation of a recently published predictive model. Clinical and demographic factors, pathology, characteristics of the biopsy procedure and visible residual lesion were recorded. T test and chi-squared test were used to identify predictors. Classification tree was used to predict upgrade. 151 patients had mean age of 53 years. The mean maximum lesion size on imaging was 11 mm. The primary atypia was ADH in 63.6%, ALH in 27.8%, and LCIS in 8.6%. 16.6% of patients had upgrade to malignancy, with 72% DCIS and 28% invasive carcinoma. Risk factors for upgrade included maximum lesion size (P = .002) and radiographic presence of residual lesion (P = .001). A predictive model based on these factors had sensitivity 78%, specificity 80% and AUC = 0.88. Validating a published nomogram with our data produced accuracy figures (AUC = 0.65) within published CI of 0.63-0.82. In CNB specimens containing ADH, ALH, or LCIS, initial lesion size and presence of residual lesion are predictors of upgrade to malignancy. A validated model may be helpful in developing patient management strategies. © 2017 Wiley Periodicals, Inc.

The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions.

PubMed

Coopey, Suzanne B; Mazzola, Emanuele; Buckley, Julliette M; Sharko, John; Belli, Ahmet K; Kim, Elizabeth M H; Polubriaginof, Fernanda; Parmigiani, Giovanni; Garber, Judy E; Smith, Barbara L; Gadd, Michele A; Specht, Michelle C; Guidi, Anthony J; Roche, Constance A; Hughes, Kevin S

2012-12-01

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diagnosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p < 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk.

Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF): benign breast tumors - short text.

PubMed

Lavoué, Vincent; Fritel, Xavier; Antoine, Martine; Beltjens, Françoise; Bendifallah, Sofiane; Boisserie-Lacroix, Martine; Boulanger, Loic; Canlorbe, Geoffroy; Catteau-Jonard, Sophie; Chabbert-Buffet, Nathalie; Chamming's, Foucauld; Chéreau, Elisabeth; Chopier, Jocelyne; Coutant, Charles; Demetz, Julie; Guilhen, Nicolas; Fauvet, Raffaele; Kerdraon, Olivier; Laas, Enora; Legendre, Guillaume; Mathelin, Carole; Nadeau, Cédric; Naggara, Isabelle Thomassin; Ngô, Charlotte; Ouldamer, Lobna; Rafii, Arash; Roedlich, Marie-Noelle; Seror, Jérémy; Séror, Jean-Yves; Touboul, Cyril; Uzan, Catherine; Daraï, Emile

2016-05-01

Screening with breast ultrasound in combination with mammography is needed to investigate a clinical breast mass (Grade B), colored single-pore breast nipple discharge (Grade C), or mastitis (Grade C). The BI-RADS system is recommended for describing and classifying abnormal breast imaging findings. For a breast abscess, a percutaneous biopsy is recommended in the case of a mass or persistent symptoms (Grade C). For mastalgia, when breast imaging is normal, no MRI or breast biopsy is recommended (Grade C). Percutaneous biopsy is recommended for a BI-RADS category 4-5 mass (Grade B). For persistent erythematous nipple or atypical eczema lesions, a nipple biopsy is recommended (Grade C). For distortion and asymmetry, a vacuum core-needle biopsy is recommended due to the risk of underestimation by simple core-needle biopsy (Grade C). For BI-RADS category 4-5 microcalcifications without any ultrasound signal, a minimum 11-G vacuum core-needle biopsy is recommended (Grade B). In the absence of microcalcifications on radiography cores additional samples are recommended (Grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial atypia, radial scar and mucocele with atypia, surgical excision is commonly recommended (Grade C). Expectant management is feasible after multidisciplinary consensus. For these lesions, when excision margins are not clear, no new excision is recommended except for LCIS characterized as pleomorphic or with necrosis (Grade C). For grade 1 phyllodes tumor, surgical resection with clear margins is recommended. For grade 2 phyllodes tumor, 10mm margins are recommended (Grade C). For papillary breast lesions without atypia, complete disappearance of the radiological signal is recommended (Grade C). For papillary breast lesions with atypia, complete surgical excision is recommended (Grade C). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells.

PubMed

Sessa, F; Bonato, M; Frigerio, B; Capella, C; Solcia, E; Prat, M; Bara, J; Samloff, I M

1990-06-01

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.

Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin.

PubMed

El Sheikh Saad, H; Meduri, G; Phrakonkham, P; Bergès, R; Vacher, S; Djallali, M; Auger, J; Canivenc-Lavier, M C; Perrot-Applanat, M

2011-07-01

The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2017-11-15

Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

PubMed

Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

2017-12-08

Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways. Published by Elsevier B.V.

Cytokeratin 5 and estrogen receptor immunohistochemistry as a useful adjunct in identifying atypical papillary lesions on breast needle core biopsy.

PubMed

Grin, Andrea; O'Malley, Frances P; Mulligan, Anna Marie

2009-11-01

The presence of atypical or usual epithelial proliferations within papillary breast lesions complicates their interpretation on core biopsy. We evaluated the combination of estrogen receptor (ER) and cytokeratin 5 (CK5) as an aid in the distinction of usual duct hyperplasia from atypical proliferations in this setting. Core biopsies from 185 papillary lesions were reviewed and of these, 82 cases were selected for immunohistochemical study based on the presence of an epithelial proliferation between the fibrovascular cores. Fifty-two cases were used as the test set and 30 cases, with subsequent surgical excision, were used as the validation set. The epithelial proliferation was evaluated for staining intensity and percentage of positive cells using CK5 and ER. Expression of both CK5 and ER was significantly different in nonatypical lesions when compared with atypical lesions (P<0.0001). Nonatypical lesions typically showed an ER-low/CK5-high profile and atypical lesions showed an ER-high/CK5-low profile with ER-high expression defined as diffuse strong staining in >90% of cells. CK5-high expression was defined as a mosaic pattern of staining in >20% of cells and CK5-low as absent or staining in <20% of cells. On the basis of their staining profile, 29 of the 30 validation cases were correctly classified using the excision specimen as the gold standard. Patterns and extent of ER and CK5 staining, when used together, are valuable adjunct stains to differentiate usual duct hyperplasia from atypical proliferations within papillary lesions on core biopsy.

[In situ adenocarcinoma of the uterus cervix: difficulties of its cytohistological diagnosis].

PubMed

Tranbaloc, P

2002-04-01

In situ adenocarcinoma is regarded as the precursor of invasive adenocarcinoma. It is asymptomatic and early diagnosis relies solely on cytopathologist. It is usually discovered on a cone for squamous CIN. When diagnosis is made by biopsy, conisation is required to exclude invasive adenocarcinoma. Lesion is histologically characterised by epitheliomatous transformation of endocervical glands without invasion of the chorion. By the appearance of glandular cells, different histological varieties are described. They have no influence on the prognosis. Several benign lesions may mimic adenocarcinoma: tubal metaplasia, glandular atypia due to inflammation or irradiation, mesonephric remnants and microglandular hyperplasia. Precursor lesions (atypical hyperplasia, glandular dysplasia, CIGNI and II) are badly morphologically defined. Preferential location of in situ adenocarcinoma is the transformation zone. Because of this topography, if the surgical margins are disease free, conisation alone may be adequate therapy. HPV infection (mainly HPV 18) are incriminated in its pathogenesis.

Telangiectatic focal nodular hyperplasia of the liver: a case detected at birth.

PubMed Central

Kim, Han-Seong; Kim, Young A.; Kim, Chong Jai; Suh, Yeon-Lim; Jang, Ja-June; Chi, Je G.

2003-01-01

A case of telangiectatic focal nodular hyperplasia (FNH) was detected at birth and was surgically removed. Grossly, the lesion was a solitary nodule and showed vague nodularity, appearing as an adenoma-like mass with fine fibrous septa, but having no macroscopic scar. On microscopic scale, the mass typically had neither fibrous central scar nor hyperplastic nodules different from the usual FNHs. The hepatic plates were separated by sinusoidal dilatation, sometimes alternating with areas of marked ectasia. Instead of large fibrous scar, thin fibrous septa were often found, and contained abnormal tortuous large arteries. These high-pressure vessels were connected directly into the adjacent sinusoids and made marked dilation of sinusoids. Bile ductular proliferation was also noted in the thin fibrous septa. To our knowledge, this is considered to be the first reported case of telangiectatic FNH detected at birth. PMID:14555832

A THEORY OF THE GENESIS OF BREAST DUCT PAPILLOMA

PubMed Central

Whang, Junshick

1960-01-01

While it is not the intent to argue that papilloma never develops in the conventionally accepted manner (proliferative growth from the wall of a pre-existing cavity) a new, perhaps alternative, genesis is suggested. The concept is that, beginning with the usual lobular structure of the breast, first by hyperplasia and then by coalescence of alveoli, seen earliest at the periphery of the lobule, spaces appear between the content of the lobule and the wall. By confluence of these spaces a larger cystic cavity is formed. Coalescence of alveoli through the body of the central mass, in the same way as at the periphery, develops the familiar pattern of “papilloma.” Following the earlier hyperplasia, regressive changes appear and may go on to complete disintegration of the papillary mass, leaving a smooth-walled cavity. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:13844252

Long-term surgical-orthodontic management of hemimandibular hyperplasia.

PubMed

Bennett, Samuel C; Goonewardene, Mithran S

2016-05-01

Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical unilateral elongation of the mandible becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and the dental compensatory mechanism is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is effectively managed by combined surgical-orthodontic care to address the facial, skeletal and dental problems that confront clinicians. Orthodontists are advised to assess patients with HH during the post-treatment retention stage for continuing mandibular growth and assess the stability of treatment outcomes with long-term follow-up and records as required. To present a case of hemimandibular hyperplasia treated successfully by combined surgical-orthodontic care and evaluated for stability over a seven-year follow-up period. Surgical-orthodontic management was accomplished in four stages: 1) pre-surgical orthodontic; 21 surgical; 3) post-surgical orthodontic; and 4) post-treatment orthodontic retention. Complete orthodontic records, including extra- and intra-oral photographs, study models, and cephalograms plus panoramic radiographs were taken at the pretreatment, post-treatment, and seven-year orthodontic retention time-points. Facial, skeletal and dental goals were achieved in the three planes of space and the long-term stability of the treatment results was shown during a post-treatment orthodontic retention period of seven years. Hemimandibular hyperplasia is a true growth anomaly which may be managed effectively. Clinicians may expect successful long-term correction and stability by utilising a comprehensive surgical-orthodontic treatment approach.

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

PubMed

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic differences exist between these two tumors that may be important for future therapeutic strategies.

Human Papillomavirus (HPV) Genotypes in Condylomas, Intraepithelial Neoplasia, and Invasive Carcinoma of the Penis Using Laser Capture Microdissection (LCM)-PCR: A Study of 191 Lesions in 43 Patients.

PubMed

Fernández-Nestosa, María J; Guimerà, Nuria; Sanchez, Diego F; Cañete-Portillo, Sofía; Velazquez, Elsa F; Jenkins, David; Quint, Wim; Cubilla, Antonio L

2017-06-01

Laser capture microdissection-polymerase chain reaction (LCM-PCR) supported by p16 was used for the first time to demonstrate human papillomavirus (HPV) DNA in histologically specific penile lesions, which were as follows: squamous hyperplasia (12 lesions, 10 patients), flat lesions (12 lesions, 5 patients), condylomas (26 lesions, 7 patients), penile intraepithelial neoplasia (PeIN) (115 lesions, 43 patients), and invasive squamous cell carcinomas (26 lesions, 26 patients). HPV was detected by whole-tissue section and LCM-PCR. LCM proved to be more precise than whole-tissue section in assigning individual genotypes to specific lesions. HPV was negative or very infrequent in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of carcinomas. HPV was strongly associated with condylomas, warty/basaloid PeIN, adjacent flat lesions, and warty/basaloid carcinomas. A single HPV genotype was found in each lesion. Some condylomas and flat lesions, especially those with atypia, were preferentially associated with high-risk HPV. Unlike invasive carcinoma, in which few genotypes of HPV were involved, there were 18 HPV genotypes in PeIN, usually HPV 16 in basaloid PeIN but marked HPV heterogeneity in warty PeIN (11 different genotypes). Variable and multiple HPV genotypes were found in multicentric PeIN, whereas unicentric PeIN was usually related to a single genotype. There was a correspondence among HPV genotypes in invasive and associated PeIN. p16 was positive in the majority of HPV-positive lesions except condylomas containing LR-HPV. p16 was usually negative in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of squamous cell carcinomas. In summary, we demonstrated that LCM-PCR was a superior research technique for investigating HPV genotypes in intraepithelial lesions. A significant finding was the heterogeneity of HPV genotypes in PeIN and the differential association of HPV genotypes with subtypes of PeIN. The presence of atypia and high-risk HPV in condylomas and adjacent flat lesions suggests a precursor role, and the correspondence of HPV genotypes in invasive carcinomas and associated PeIN indicates a causal relation. Data presented support the bimodal hypothesis of penile cancer carcinogenesis in HPV-driven and non-HPV-driven carcinomas and justify the current WHO pathologic classification of PeIN in special subtypes.

Breast cancer metastasis to the stomach resembling early gastric cancer.

PubMed

Eo, Wan Kyu

2008-12-01

Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infiltrating ductal carcinoma (IDC) of the breast in a 48-year-old woman. The patient had undergone a left modified radical mastectomy with axillary dissection nine years prior. A gastric endoscopy performed for evaluation of nausea and anorexia showed the presence of a slightly elevated mucosal lesion in the cardia, suggestive of a type IIa EGC. A histological examination revealed nests of a carcinoma in the subepithelial lymphatics, and immunohistochemical staining for estrogen receptor was positive. This is an extremely rare case with features of type IIa EGC, but the lesion was finally identified as a cancer metastasis to the cardia of the stomach from an IDC of the breast.

Role of HGF in epithelial–stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ

PubMed Central

2013-01-01

Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that targeting stroma-derived HGF signaling in early carcinogenesis may block progression of basal-like precursor lesions. PMID:24025166

[Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (dipnech) - an overview of the cases diagnosed at the department of thoracic surgery in the years 2010-2014].

PubMed

Stefański, Mariusz; Bruliński, Krzysztof; Stefańska, Marianna

Pulmonary neuroendocrine cells (PNEC) are present in the normal lungs with the incidence of 1 in 2500 epithelial cells. They usually proliferate in the presence of reactive processes related to inflammation and fibrosis of the lung parenchyma. The division of pulmonary neuroendocrine cell hyperplasia proposed by Travis et al. additionally distinguished diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) or proliferation that occurs in people without reactive hyperplasia risk factors. The confirmation of the DIPNECH diagnosis requires staining of biopsy specimens using the immunohistochemical technique for neuroendocrine markers. The aim of this study is to overview the cases of 5 patients in whom the histopathological DIPNECH diagnosis was made in the process of invasive diagnostics performed at the Department of Thoracic Surgery. The aim of the study is to evaluate typical clinical, functional, radiological and histopathological features of this rare disease syndrome. In the period from April 2010 to June 2014, five patients with lesions in the lungs were subjected to invasive diagnostics. Histopathological and immunohistochemical examinations of the collected specimens were used to make the DIPNECH diagnosis in these patients. The natural history of the disease was traced based on a 5-year follow-up in one of the patients. In addition, we analyzed the literature with regard to the described cases. Thanks to the early diagnosis of non-specific lesions in the lungs, typical carcinoid which develops on the basis of discussed DIPNECH, was found in the resected material in two out of five operated patients. The accurate diagnosis of DIPNECH allows for the implementation of appropriate treatment and channels further management of the patient into the right direction.

Comparison of Anti BPH capsule (herbal) and Terazosin HCl in the treatment of benign prostate hyperplasia.

PubMed

Nadeem, Hafiz Mohammad Rashid; Mohiuddin, Ejaz; UdDin, Shahab; Daniyal, Muhammad; Usmanghani, Khan

2017-01-01

Benign prostatic hyperplasia (BPH) is a disease of senile age, usually occurring> 60 years of age. BPH is a disease that involves cell proliferation of the prostate. Pathological hyperplasia affects the elements of the glandular and connective tissue of the prostate. This study is designed to scrutinize the efficacy and tolerability of herbal drug Anti BPH capsule for the management of benign prostate hyperplasia (BPH), in this study we select the 100 patients in which 50 received the Anti BPH capsule and 50 received the Terazosin HCl. We use the American Urological Association BPH Symptom Score Index Questionnaire to measure the quality of life of the patients. We compare the before treatment and after treatment results for each symptom. We record the following symptoms, incomplete emptying of bladder, Frequency, Intermittency, Urgency, Weak stream, Straining, Nocturia and weight of prostate gland by USG. We compare the both drug by using paired sample t-test. The level of significance of incomplete emptying of bladder before treatment and after treatment is 0.013 in test group and 0.032 in control group. Similarly the level of significance of Frequency before treatment and after treatment in test groups in, intermittency, Urgency, Weak stream, staining, Nocturia and mean weight of prostate gland are 0.007, 0.015, 0.044, 0.012, 0.017, 0.004 and 0.020; where as in control group afford as 0.031, 0.044, 0.044, 0.032, 0.024, 0.009 and 0.035 respectively. The herbal drug Anti BPH capsule is more effective in the treatment of BPH than Allopathic medicine Terazosin HCl.

Preventive effects of fermented brown rice and rice bran against N-nitrosobis (2-oxopropyl) amine-induced pancreatic tumorigenesis in male hamsters.

PubMed

Kuno, Toshiya; Takahashi, Satoru; Tomita, Hiroyuki; Hisamatsu, Kenji; Hara, Akira; Hirata, Akihiro; Kobayashi, Hiroshi; Mori, Hideki

2015-12-01

Fermented brown rice by Aspergillus oryzae (FBRA) is known to have the potential to prevent chemical carcinogenesis of the colon, liver, esophagus, urinary bladder, stomach and lungs in rodents. The present study examined the possible chemopreventive effects of FBRA on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumorigenesis in hamsters. Five-week-old male Syrian golden hamsters were divided into seven groups. Groups 1-5 were subcutaneously injected with BOP (10 mg/kg body weight) four times during week 6 to induce pancreatic tumors, while groups 6 and 7 were injected with saline. Groups 2 and 3 were fed diets containing 5 and 10% FBRA, respectively, during the initiation phase. By contrast, groups 4 and 5 were fed diets containing 5 and 10% FBRA, respectively, during the post-initiation phase. Group 6 received a diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as the untreated control. At the termination of the study (week 22), oral intake of 10% FBRA (group 5) during the post-initiation phase was identified to have significantly reduced the multiplicity (number of lesions/animal) of ductal adenocarcinoma [pancreatic intraepithelial neoplasia 3 (PanIN3); carcinoma in situ and invasive carcinoma] in comparison with group 1 control hamsters (0.24±0.44 vs. 0.71±0.72; P<0.05). Treatment with 10% FBRA in the post-initiation phase inhibited the progression of normal/precancerous lesions (PanIN1, mild hyperplastic lesions; and PanIN2, papillary hyperplasia) to ductal adenocarcinomas. Furthermore, dietary exposure to 10% FBRA during the initiation (group 3) and post-initiation phases (group 5) significantly reduced the multiplicity of PanIN2 (group 3, 0.55±0.69; group 5, 0.45±0.69; versus group 1, 1.26±1.24; P<0.05 and P<0.01, respectively). A significant reduction of Ki-67 positivity of PanIN2 in group 5 was also confirmed (group 5, 0.05±0.03; group 1, 0.22±0.12; P<0.01). Using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, augmentation of apoptosis by FBRA exposure in the non-lesional ductal epithelium and proliferative lesions was not evident. These findings indicate that FBRA exhibits inhibitory effects on BOP-induced pancreatic tumorigenesis in hamsters due to the reduced proliferation rate of tumor cells. Thus, FBRA may be a promising chemopreventive agent in human pancreatic cancer.

Effects of large pressure amplitude low frequency noise in the parotid gland perivasculo-ductal connective tissue.

PubMed

Oliveira, Pedro; Brito, José; Mendes, João; da Fonseca, Jorge; Águas, Artur; Martins dos Santos, José

2013-01-01

In tissues and organs exposed to large pressure amplitude low frequency noise fibrosis occurs in the absence of inflammatory signs, which is thought to be a protective response. In the parotid gland the perivasculo-ductal connective tissue surrounds arteries, veins and the ductal tree. Perivasculo-ductal connective tissue is believed to function as a mechanical stabilizer of the glandular tissue. In order to quantify the proliferation of perivasculo-ductal connective tissue in large pressure amplitude low frequency noise-exposed rats we used sixty Wistar rats which were equally divided into 6 groups. One group kept in silence, and the remaining five exposed to continuous large pressure amplitude low frequency noise: g1-168h (1 week); g2-504h (3 weeks); g3-840h (5 weeks); g4-1512h (9 weeks); and g5-2184h (13 weeks). After exposure, parotid glands were removed and the perivasculo-ductal connective tissue area was measured in all groups. We applied ANOVA statistical analysis, using SPSS 13.0. The global trend is an increase in the average perivasculo-ductal connective tissue areas, that develops linearly and significantly with large pressure amplitude low frequency noise exposure time (p < 0.001). It has been suggested that the biological response to large pressure amplitude low frequency noise exposure is associated with the need to maintain structural integrity. The structural reinforcement would be achieved by increased perivasculo-ductal connective tissue. Hence, these results show that in response to large pressure amplitude low frequency noise exposure, rat parotid glands increase their perivasculo-ductal connective tissue.

Pharmacodynamics and Medicinal Chemistry of an External Chinese Herbal Formula for Mammary Precancerous Lesions

PubMed Central

Zhang, Guijuan; Ma, Yi; Fan, Hongxia

2017-01-01

Ruyan Neixiao Cream (RYNXC) is a traditional Chinese herbal formula for treating mammary precancerous disease. This study was carried out to investigate in vivo anticancer effect of RYNXC and multiple constituents. 32 virginal Sprague-Dawley rats were randomly divided into blank control group (BC), mammary precancer models group (MODEL), tamoxifen group (TAM), and Ruyan Neixiao Cream group (RYNXC). TAM was intervened by tamoxifen; RYNXC was intervened by Ruyan Neixiao Cream. The chromatographic separation was performed by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). RYNXC showed significant improvement in erythrocyte aggregation index (EAI), hematocrit (HCT), fibrinogen (FIB), spleen coefficient, and uterus coefficient compared with MODEL. In RYNXC and TAM groups, atypical hyperplasia was observed in pathological mammary tissues; meanwhile in MODEL group, ductal carcinoma was observed in situ. Moreover, fifteen compounds were characterized according to HPLC-MS data, including organic acids, tannin, alkaloid, volatile oil, anthraquinones, and flavonoids. The study suggests that RYNXC was an effective Chinese herbal formula for mammary precancerous lesions and provides a scientific basis for the quality standard and the pharmacology of RYNXC. It will be beneficial to the future clinical application of RYNXC. PMID:28811827

First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

PubMed

Rageth, Christoph J; O'Flynn, Elizabeth Am; Comstock, Christopher; Kurtz, Claudia; Kubik, Rahel; Madjar, Helmut; Lepori, Domenico; Kampmann, Gert; Mundinger, Alexander; Baege, Astrid; Decker, Thomas; Hosch, Stefanie; Tausch, Christoph; Delaloye, Jean-François; Morris, Elisabeth; Varga, Zsuzsanna

2016-09-01

The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision.

Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

PubMed Central

Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr

2011-01-01

Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH. PMID:21472097

Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias.

PubMed

Miettinen, M

1981-03-01

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re-examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85--95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.

Massive thymic hemorrhage and hemothorax occurring in utero.

PubMed

Gargano, Giancarlo; Paltrinieri, Anna Lucia; Gallo, Claudio; Di Pancrazio, Luciana; Roversi, Maria Federica; Ferrari, Fabrizio

2015-11-14

Thymic enlargement is a common and physiological finding in children and neonates' X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good. Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality. We report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax. Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary. Thymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress.

Angiolymphoid hyperplasia with eosinophilia-acquired port-wine-stain-like lesions: attempt at treatment with the argon laser.

PubMed

Pasyk, K A; Elsenety, E N; Schelbert, E B

1988-01-01

An unusual case of angiolymphoid hyperplasia with eosinophilia (ALHE) simulating port-wine stain in a 50-year-old woman is reported. The lesions of ALHE are typically papules or subcutaneous masses that range from light pink to red-brown in color. In addition to the usual histologic findings of ALHE, the biopsy in our patient showed some fibrin-like material and fibrous long-spacing collagen on ultrastructural examination. This unusual lesion necessitates biopsy because the differential diagnosis includes port-wine stain, sarcoidosis, lupus erythematosus, and non-Hodgkin lymphoma (mycosis fungoides). Many different forms of treatment have been attempted for ALHE including radiotherapy, cytotoxic chemotherapy, corticosteroids, and antibiotics. The lesions in our patient responded to argon laser therapy and surgical excision, though there has been recurrence on the border of the treated area. Because laser energy is noncumulative in the tissues and effective in removing the lesions, we recommend it as the treatment of choice for these lesions.

Parathyroid hyperplasia

MedlinePlus

Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic kidney disease - parathyroid hyperplasia; ...

Radiocontrast Dye Extravasation During Sialography.

PubMed

Truong, Kristy; Hoffman, Henry T; Policeni, Bruno; Maley, Joan

2018-03-01

Evaluate the pathophysiology of contrast extravasation. Two hundred fifty-five sialograms at the University of Iowa from 2008 to 2016 were reviewed. Twelve sialograms (4.7% of total) were identified with main ductal extravasation. In each case, ductal stenosis as a diagnosis was supported by clinical history and the finding of difficulty in advancing the cannula into the duct during sialography. In all but 1 case, extravasation occurred at the distal duct with no further imaging of the ductal system. Each of the 5 cases treated with sialendoscopy with or without gland resection confirmed stenosis. Ultrasound evaluation of 5 of the cases detected ductal dilation in 4 (80%). Six of 11 computed tomography scans done before the sialogram were interpreted as normal with indirect evidence for ductal stenosis (duct dilation) reported in only 1. All extravasations were associated with either stricture alone or stricture with stone (1 case). Radiocontrast extravasation from the main duct during sialography is highly associated with the presence of ductal stricture. In our experience, the inability to fill the ductal system with radiocontrast is a useful sialographic finding that correlated closely with anatomic abnormality rather than technical error. The frequent finding of extravasation of radiocontrast supports the use of water soluble contrast.

Culturing primary mouse pancreatic ductal cells.

PubMed

Reichert, Maximilian; Rhim, Andrew D; Rustgi, Anil K

2015-06-01

The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). PDAC resembles ductal cells morphologically. To study pancreatic ductal cell (PDC) and pancreatic intraepithelial neoplasia (PanIN)/PDAC biology, it is essential to have reliable in vitro culture conditions. Here we describe a methodology to isolate, culture, and passage PDCs and duct-like cells from the mouse pancreas. It can be used to isolate cells from genetically engineered mouse models (GEMMs), providing a valuable tool to study disease models in vitro to complement in vivo findings. The culture conditions allow epithelial cells to outgrow fibroblast and other "contaminating" cell types within a few passages. However, the resulting cultures, although mostly epithelial, are not completely devoid of fibroblasts. Regardless, this protocol provides guidelines for a robust in vitro culture system to isolate, maintain, and expand primary pancreatic ductal epithelial cells. It can be applied to virtually all GEMMs of pancreatic disease and other diseases and cancers that arise from ductal structures. Because most carcinomas resemble ductal structures, this protocol has utility in the study of other cancers in addition to PDAC, such as breast and prostate cancers. © 2015 Cold Spring Harbor Laboratory Press.

The risk of breast cancer associated with specific patterns of migraine history

PubMed Central

Lowry, Sarah J.; Malone, Kathleen E.; Cushing-Haugen, Kara L.; Li, Christopher I.

2014-01-01

Purpose Studies have suggested that a history of migraines may be associated with a lower risk of some types of breast cancer, though biological mechanisms are unclear. Identifying specific characteristics of migraines which are most strongly associated with breast cancer risk could improve our understanding of this relationship. Methods We ascertained specific characteristics of women's migraine histories (severity, timing features, presence of migraine aura). We used polytomous logistic regression to estimate the risk of ER+ ductal, ER- ductal, ER+ lobular, and ER+ ductal-lobular breast cancer associated with self-reported characteristics of migraine history. 715 breast cancer cases (276 ER+ ductal, 46 ER- ductal, 191 ER+ lobular, 202 ER+ ductal-lobular) and 376 controls ages 55-74 years were included in this population-based case-control study. Results Compared to women without a migraine history, women with a >30-year history of migraines had a 60% (95% CI: 0.2-0.6) lower risk of ER+ ductal breast cancer; those who had their first migraine before age 20 had 50% lower risks of ER+ ductal and ER+ lobular breast cancer (both 95%CIs: 0.3-0.9), and women who experienced migraine with aura had 30% (95%CI 0.5-0.98) and 40% (95%CI: 0.4-0.9) lower risks of ER+ ductal and ER+ lobular breast cancer, respectively. Conclusion The lower risk of ER+ breast cancer associated with migraine appears to be limited to those women with early onset or long duration of migraine history, or those who experienced migraine with aura. This expands our understanding of the relationship between migraine and breast cancer and provides additional insight into potential underlying biological mechanisms. PMID:25359301

International Registry for Patients With Castleman Disease

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia, Giant Lymph Node; Lymph Node Hyperplasia, Giant

Consistency of histopathological reporting of breast lesions detected by screening: findings of the U.K. National External Quality Assessment (EQA) Scheme. U. K. National Coordinating Group for Breast Screening Pathology.

PubMed

Sloane, J P; Ellman, R; Anderson, T J; Brown, C L; Coyne, J; Dallimore, N S; Davies, J D; Eakins, D; Ellis, I O; Elston, C W

1994-01-01

The aim of the scheme was to determine consistency of histopathological reporting in the United Kingdom National Breast Screening Programme. This external quality assessment scheme involved 51 sets of 12 slides which were circulated to 186-251 pathologists at intervals of 6 months for 3 years. Participants recorded their diagnoses on standard reporting forms, which were submitted to the U.K. National Cancer Screening Evaluation Unit for analysis. A high level of consistency was achieved in diagnosing major categories of breast disease including invasive carcinoma and the important borderline lesions, radial scar and ductal carcinoma in situ (DCIS), the latter exceeding a national target set prior to the onset of the scheme. Atypical hyperplasia (AH) was reported with much less consistency although, where it was the majority opinion, over 86% of diagnoses were of benign disorders and only 14% were of DCIS. Inconsistency was encountered in subtyping and measuring DCIS, the former apparently due to current uncertainties about classification and the latter to poor circumscription, variation in size in different sections and merging with zones of AH. Reporting prognostic features of invasive carcinomas was variable. Measurement of size was achieved with adequate consistency except in a small number of very poorly circumscribed tumours. Grading and subtyping were inconsistent although the latter was not specifically tested and will be the subject of future study. Members of the National Coordinating Group achieved greater uniformity than the remainder of the participants in all diagnostic categories, but both groups experienced similar types of problem. Our findings suggest that participation in the scheme improves diagnostic consistency. In conclusion, consistency in diagnosing invasive carcinoma and radial scar is excellent, and good in DCIS, but improvements are desirable in diagnosing atypical hyperplasia, classifying DCIS and reporting certain prognostic features of invasive tumours. Such improvements will require further research, the development of improved diagnostic criteria and the dissemination of clearer guidelines.

Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma

PubMed Central

Castro, Nadia P; Osório, Cynthia ABT; Torres, César; Bastos, Elen P; Mourão-Neto, Mário; Soares, Fernando A; Brentani, Helena P; Carraro, Dirce M

2008-01-01

Introduction Ductal carcinoma in situ (DCIS) of the breast includes a heterogeneous group of preinvasive tumors with uncertain evolution. Definition of the molecular factors necessary for progression to invasive disease is crucial to determining which lesions are likely to become invasive. To obtain insight into the molecular basis of DCIS, we compared the gene expression pattern of cells from the following samples: non-neoplastic, pure DCIS, in situ component of lesions with co-existing invasive ductal carcinoma, and invasive ductal carcinoma. Methods Forty-one samples were evaluated: four non-neoplastic, five pure DCIS, 22 in situ component of lesions with co-existing invasive ductal carcinoma, and 10 invasive ductal carcinoma. Pure cell populations were isolated using laser microdissection. Total RNA was purified, DNase treated, and amplified using the T7-based method. Microarray analysis was conducted using a customized cDNA platform. The concept of molecular divergence was applied to classify the sample groups using analysis of variance followed by Tukey's test. Results Among the tumor sample groups, cells from pure DCIS exhibited the most divergent molecular profile, consequently identifying cells from in situ component of lesions with co-existing invasive ductal carcinoma as very similar to cells from invasive lesions. Additionally, we identified 147 genes that were differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma, which can discriminate samples representative of in situ component of lesions with co-existing invasive ductal carcinoma from 60% of pure DCIS samples. A gene subset was evaluated using quantitative RT-PCR, which confirmed differential expression for 62.5% and 60.0% of them using initial and partial independent sample groups, respectively. Among these genes, LOX and SULF-1 exhibited features that identify them as potential participants in the malignant process of DCIS. Conclusions We identified new genes that are potentially involved in the malignant transformation of DCIS, and our findings strongly suggest that cells from the in situ component of lesions with co-existing invasive ductal carcinoma exhibit molecular alterations that enable them to invade the surrounding tissue before morphological changes in the lesion become apparent. PMID:18928525

Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma.

PubMed

Castro, Nadia P; Osório, Cynthia A B T; Torres, César; Bastos, Elen P; Mourão-Neto, Mário; Soares, Fernando A; Brentani, Helena P; Carraro, Dirce M

2008-01-01

Ductal carcinoma in situ (DCIS) of the breast includes a heterogeneous group of preinvasive tumors with uncertain evolution. Definition of the molecular factors necessary for progression to invasive disease is crucial to determining which lesions are likely to become invasive. To obtain insight into the molecular basis of DCIS, we compared the gene expression pattern of cells from the following samples: non-neoplastic, pure DCIS, in situ component of lesions with co-existing invasive ductal carcinoma, and invasive ductal carcinoma. Forty-one samples were evaluated: four non-neoplastic, five pure DCIS, 22 in situ component of lesions with co-existing invasive ductal carcinoma, and 10 invasive ductal carcinoma. Pure cell populations were isolated using laser microdissection. Total RNA was purified, DNase treated, and amplified using the T7-based method. Microarray analysis was conducted using a customized cDNA platform. The concept of molecular divergence was applied to classify the sample groups using analysis of variance followed by Tukey's test. Among the tumor sample groups, cells from pure DCIS exhibited the most divergent molecular profile, consequently identifying cells from in situ component of lesions with co-existing invasive ductal carcinoma as very similar to cells from invasive lesions. Additionally, we identified 147 genes that were differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma, which can discriminate samples representative of in situ component of lesions with co-existing invasive ductal carcinoma from 60% of pure DCIS samples. A gene subset was evaluated using quantitative RT-PCR, which confirmed differential expression for 62.5% and 60.0% of them using initial and partial independent sample groups, respectively. Among these genes, LOX and SULF-1 exhibited features that identify them as potential participants in the malignant process of DCIS. We identified new genes that are potentially involved in the malignant transformation of DCIS, and our findings strongly suggest that cells from the in situ component of lesions with co-existing invasive ductal carcinoma exhibit molecular alterations that enable them to invade the surrounding tissue before morphological changes in the lesion become apparent.

Castleman Disease Collaborative Network Biobank

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia; Giant Lymph Node

An Interesting Case of Oral Inverted Ductal Papilloma.

PubMed

Berridge, Natasha; Kumar, Mahesh

2016-12-01

Ductal papillomas are rare benign papillary tumours of the minor salivary glands. Previously they have been classified into three subtypes: inverted ductal papilloma (IDP), sialadenoma papilliferum and intraductal papilloma. The oral inverted ductal papilloma is the least common of these lesions, with 48 cases reported to date in a search of the English-language literature. We describe an interesting case of oral IDP and highlight the pertinent clinical and histopathological features. Importantly, unlike the histologically similar inverted papilloma (IP) of the nose and paranasal sinuses, oral IDP is a completely benign lesion and is not associated with malignant change. Clinical relevance: This case report aims to raise awareness of the lesion, oral inverted ductal papilloma (IDP). We outline the clinical features and unique histopathology of oral IDP so that clinicians may correctly diagnose such a lesion and implement appropriate treatment.

Histopathology of Veins Obtained at Hemodialysis Arteriovenous Fistula Creation Surgery.

PubMed

Alpers, Charles E; Imrey, Peter B; Hudkins, Kelly L; Wietecha, Tomasz A; Radeva, Milena; Allon, Michael; Cheung, Alfred K; Dember, Laura M; Roy-Chaudhury, Prabir; Shiu, Yan-Ting; Terry, Christi M; Farber, Alik; Beck, Gerald J; Feldman, Harold I; Kusek, John W; Himmelfarb, Jonathan

2017-10-01

Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α -smooth muscle actin-expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort. Copyright © 2017 by the American Society of Nephrology.

Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

PubMed Central

2012-01-01

Background Lysine-specific demethylase1 (LSD1) is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS) in comparison to invasive ductal breast cancer (IDC). Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27), intermediate grade DCIS (n = 30), high grade DCIS (n = 31) and in invasive ductal breast cancer (n = 32). SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event. PMID:22920283

Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast.

PubMed

Serce, Nuran; Gnatzy, Annette; Steiner, Susanne; Lorenzen, Henning; Kirfel, Jutta; Buettner, Reinhard

2012-08-24

Lysine-specific demethylase1 (LSD1) is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS) in comparison to invasive ductal breast cancer (IDC). Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27), intermediate grade DCIS (n = 30), high grade DCIS (n = 31) and in invasive ductal breast cancer (n = 32). SPSS version 18.0 was used for statistical analysis. LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

Ductal carcinoma of the parotid gland.

PubMed

Eriksen, H E; Greisen, O; Hastrup, N

1987-06-01

A case of ductal carcinoma of the parotid gland is described. The medical literature contains only 13 previous reports on this kind of adenocarcinoma of the parotid gland. The tumour is characterized by its histologic resemblance to ductal carcinomas of the breast and prostate. The course of previously described cases suggests that this tumour has a highly aggressive biological behaviour.

Youngest case of ductal carcinoma in situ arising within a benign phyllodes tumour: A case report.

PubMed

Chopra, Sharat; Muralikrishnan, Vummiti; Brotto, Maurizio

2016-01-01

Phyllodes tumour (PT) is a rare tumour of the female breast. The tumour clinically and radiologically mimics the features of a fibroadenoma. Ductal carcinoma in situ (DCIS) in the epithelial component of PT is a very rare finding. We present youngest ever case of a 23-year-old nulliparous woman with high-grade ductal carcinoma in situ arising within a benign phyllodes tumor. Macroscopically, it is a homogeneous tumour with solid components. Microscopically, it features typical leaf-like pattern with hypercellular stroma with high-grade ductal carcinoma in situ. To date, eight such rare cases of benign phyllodes tumour with ductal carcinoma in situ have been documented. We report the youngest case known in literature so far. As this is a very rare presentation, it poses several challenges in regard to both management and follow-up. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Synchronous bilateral breast cancer in a male].

PubMed

García-Mejido, José Antonio; Delgado-Jiménez, Carmen; Gutiérrez-Palomino, Laura; Sánchez-Sevilla, Miguel; Iglesias-Bravo, Eva; Caballero-Fernández, Virginia

2013-01-01

male breast cancer is a disease with low incidence, which is further reduced when it comes to bilateral synchronous presentation. There are few published cases in recent years. The aim is to establish guidelines for the management of this disorder that is so rare. a 75-year-old with tumors in both breasts, which were completely resected with removal of palpable nodes. The histopathological study reported ductal carcinoma. The indicated treatment was adjuvant tamoxifen and radiotherapy. The patient is currently in a disease-free period. this is a rare disease, whose main treatment is surgery, hence the importance of early diagnosis. Most cases require adjuvant chemotherapy and radiotherapy because they are usually diagnosed at an advanced stage.

Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

PubMed

Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad; Adib, Ali

2016-01-01

Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

A High Ductal Flow Velocity Is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22–27 Weeks Gestational Age

PubMed Central

Olsson, Karl Wilhelm; Jonzon, Anders; Sindelar, Richard

2012-01-01

Objective. To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22–27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors. Method. Infants born at 22–27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory, and outcome parameters. Echocardiographic examinations during treatment were reviewed. Results. Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25 + 4 weeks versus 24 + 3 weeks; P = 0.047), and a higher pretreatment left to right maximal ductal flow velocity (1.6 m/s versus 1.1 m/s; P = 0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at start of treatment, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04; P = 0.049). Conclusion. Maximal ductal flow velocity was independently associated with success of PDA treatment. PMID:23316351

Familial endocrine myxolentiginosis.

PubMed

Panossian, D H; Marais, G E; Marais, H J

1995-11-01

We present an unusual case of a left atrial myxoma as a feature of a familial mesoectodermal disorder and review the literature. The new term "familial endocrine myxolentiginosis" is proposed, which is descriptive of the major clinical components of the syndrome. Myriad features of this disorder include (1) cardiac myxomas; (2) cutaneous myxomas; (3) multiple lentigines or blue nevi, particularly of the head and neck; (4) bilateral primary pigmented nodular adrenocortical hyperplasia; (5) unusual testicular tumors; (6) pituitary tumors; (7) myxoid fibroadenomas of the breast; (8) myxomatous disorder of the stroma of the breast; (9) ductal adenoma of the breast; and (10) psammomatous melanotic schwannoma. A tentative diagnosis is suggested by identifying two features and a definitive diagnosis is made by three or more features. The clinical and pathologic features of cardiac myxoma in familial endocrine myxolentiginosis are identical to those of familial cardiac myxoma: age < 40 years, atypical locations, multicentric origins, and recurrent presentations. A Venn diagram classification for cardiac myxomas is proposed. We include photographic, echocardiographic, biopsy, and adrenal computerized tomography documentation in our patient. Recognition of this disorder is important because of its clinical, surgical, and genetic implications. The availability of transesophageal echocardiographic technology should allow early diagnosis of this underdiagnosed entity. Clinicians should consider this entity in the differential diagnosis of their patients with any one of these manifestations.

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2009-10-01

AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2008 – 14 September 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth Inhibitor...9 Fibroblast Growth Factor -2: an Epithelial Ductal Cell Growth Inhibitor that Drops Out in Breast Cancer

Pre- and Post-ductal oxygen saturation among apparently healthy low birth weight neonates.

PubMed

Odudu, Leo A; Ezenwa, Beatrice N; Esezobor, Christopher I; Ekure, Ekanem N; Egri Okwaji, Mathias T C; Ezeaka, Chinyere V; Njokanma, Fidelis O; Ladele, Jejelola

2017-01-01

Reference values of oxygen saturation (SpO2) to guide care of low birth weight neonates have been obtained mainly from Caucasians. Data from African newborns are lacking. To determine the pre- and post-ductal SpO2values of low birth weight neonates within the first 72 h of life, compare SpO2values of moderate-late preterm and term low birth weight neonates and determine how mode of delivery affected SpO2in the first 24 h of life. An observational descriptive study was carried out on apparently healthy low birth weight newborns weighing 1500 to ≤2499 g. Pre and post ductal SpO2values were recorded at the following hours of life: 10-24 h, >24-48 h and >48-72 h using a NONIN® pulse oximeter. The ranges of pre- and post-ductal SpO2in the study were similar for both preterm and term neonates in the study (89%-100%). The mean (standard deviation [SD]) pre-ductal SpO2was 95.9% (2.3) and the mean (SD) post-ductal SpO2was 95.9% (2.1). There was a significant increase in pre-ductal SpO2from 10 to 24 h through >48-72 h of life (P = 0.027). The mode of delivery did not affect SpO2values within 10-24 h of life. The present study documented daily single pre- and post-ductal SpO2 values for preterm and term low birth weight neonates weighing 1500 g to <2500 g during the first 72 h of life. The overall range and mean pre- and post-ductal SpO2 were similar for both categories of stable low birth weight neonates in the study. There was no significant difference between SpO2ranges for late preterm compared to term low birth weight neonates. The results obtained could serve as guide in assessing SpO2of low birth weight neonates weighing between 1500 and 2499 g in the first 72 h of life.

Paleoandrology and prostatic hyperplasia in Italian mummies (XV-XIX century).

PubMed

Fornaciari, G; Ciranni, R; Ventura, L

2001-01-01

Prostatic hyperplasia, a very common condition today, was well known in the past as cause for bladder distension. The difficulty to identify, at autopsy of natural or artificial mummies, even a normal-sized prostate is probably the result of putrefaction processes and its usually dramatic size reduction as well. We report two ancient cases of prostatic hyperplasia recently observed in natural mummies from Italy. The first case regards Pandolfo III Malatesta (1370-1427), a leading figure of the Italian Renaissance. He was a valiant soldier and horseman with a very active life style. The tomb, containing his naturally mummified body, has recently been discovered in Fano (Marche, Central Italy). After careful X-ray and videographic examination, the autopsy showed good preservation of the skeletal muscles, cartilage, internal and external organs, included prostate gland and penis. Macroscopic examination revealed a staghorn calculus (calcium urate) of the left kidney and a severe enlargement of the prostate, with calcifications detectable by X-ray and large nodules protruding in the lumen of an ectatic urethra. Histology shows fibrous brands of connective and muscular tissue surrounding circular and oblong lacunae, with no preservation of epithelial structures. The macroscopic and histological picture allowed us to diagnose prostatic nodular hyperplasia. The second case (XIX century) concerns the natural mummy of an anonymous 50-60 years old man, found in ancient friary near L'Aquila (central Italy), which underwent computed tomography and a complete autopsy. Pelvic CT scans showed distended urinary bladder and a ring of dense tissue at the site of the prostate. At autopsy the bladder measured 7 x 6 x 5 cm and the prostate was 4 x 5 x 3 cm; prostatic urethra had a diameter of x 2 cm. Histology revealed dense fibrous tissue containing muscular fibers and roundish cavities of variable size, filled with eosinophil, PAS-positive material. Concretions were also present in some of these spaces. Strong immunohistochemical reactivy for PSA was observed in this material. The existence of glandular structures containing eosinophil, PAS-positive material, immunoreactive for PSA, confirmed the prostatic nature of the specimen, already suspected after CT scan and gross examination. The presence itself of the prostate, its histological picture, the preserved and distended urinary bladder, in addition to the age of the subject, supported the diagnosis of prostatic hyperplasia.

Dietary patterns and risk of ductal carcinoma of the breast: a factor analysis in Uruguay.

PubMed

Ronco, Alvaro L; De Stefani, Eduardo; Deneo-Pellegrini, Hugo; Boffetta, Paolo; Aune, Dagfinn; Silva, Cecilia; Landó, Gabriel; Luaces, María E; Acosta, Gisele; Mendilaharsu, María

2010-01-01

Breast cancer (BC) shows very high incidence rates in Uruguayan women. The present factor analysis of ductal carcinoma of the breast, the most frequent histological type of this malignancy both in Uruguay and in the World, was conducted at a prepaid hospital of Montevideo, Uruguay. We identified 111 cases with ductal BC and 222 controls with normal mammograms. A factor analysis was conducted using 39 food groups, allowing retention of six factors analyzed through logistic regression in order to obtain odds ratios (OR) associated with ductal BC. The low fat and non-alcoholic beverage patterns were inversely associated (OR=0.30 and OR=0.45, respectively) with risk. Conversely, the fatty cheese pattern was positively associated (OR=4.17) as well as the fried white meat (OR=2.28) and Western patterns (OR 2.13). Ductal BC shared similar dietary risk patterns as those identified by studies not discriminating between histologic type of breast cancer.

Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

PubMed Central

Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

2014-01-01

OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia. PMID:24555583

Breast imaging in patients with nipple discharge

PubMed Central

de Paula, Ivie Braga; Campos, Adriene Moraes

2017-01-01

Nipple discharge is a common symptom in clinical practice, representing the third leading breast complaint, after pain and lumps. It is usually limited and has a benign etiology. The risk of malignancy is higher when the discharge is uniductal, unilateral, spontaneous, persistent, bloody, or serous, as well as when it is accompanied by a breast mass. The most common causes of pathologic nipple discharge are papilloma and ductal ectasia. However, there is a 5% risk of malignancy, mainly ductal carcinoma in situ. The clinical examination is an essential part of the patient evaluation, allowing benign nipple discharge to be distinguished from suspicious nipple discharge, which calls for imaging. Mammography and ultrasound should be used together as first-line imaging methods. However, mammography has low sensitivity in cases of nipple discharge, because, typically, the lesions are small, are retroareolar, and contain no calcifications. Because the reported sensitivity and specificity of ultrasound, it is important to use the correct technique to search for intraductal lesions in the retroareolar region. Recent studies recommend the use of magnetic resonance imaging in cases of suspicious nipple discharge in which the mammography and ultrasound findings are normal. The most common magnetic resonance imaging finding is non-mass enhancement. Surgery is no longer the only solution for patients with suspicious nipple discharge, because short-time follow-up can be safely proposed. PMID:29307929

Clinicopathological correlates of adrenal Cushing's syndrome.

PubMed

Duan, Kai; Hernandez, Karen Gomez; Mete, Ozgur

2015-06-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinicopathological correlates of adrenal Cushing's syndrome.

PubMed

Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

2015-03-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Papillary proliferation of the endometrium: a clinicopathologic study of 59 cases of simple and complex papillae without cytologic atypia.

PubMed

Ip, Philip P C; Irving, Julie A; McCluggage, W Glenn; Clement, Philip B; Young, Robert H

2013-02-01

Papillary proliferation of the endometrium (PPE) without cytologic atypia is uncommon and has only been studied in detail by Lehman and Hart in 2001. On histologic examination, PPE ranges from simple papillae with fibrovascular cores, often involving the surface of endometrial polyps, to complex intracystic proliferations; some consider the latter to be analogous to nonatypical complex hyperplasia. To further characterize PPE, with emphasis on the risk of and features associated with concurrent or subsequent neoplasia, the clinicopathologic features of 59 cases without cytologic atypia were studied. The cases were classified into 2 groups according to the degree of architectural complexity and extent of proliferation. Group 1 consisted of those with localized simple papillae. Simple papillae were defined as those with short, predominantly nonbranching stalks; those with occasional secondary branches and/or detached papillae were also included in this group. Localized proliferations were those with 1 or 2 foci involving the surface or the subjacent glands of polyps or nonpolypoid endometrium. Group 2 consisted of those with complex papillae and/or those with diffuse and crowded intracystic papillae. Complex papillae were those with either short or long stalks, with frequent secondary and complex branches. Diffuse proliferation was defined as presence of 3 or more foci within a specimen or involvement of >50% of the endometrial polyp by simple or complex PPE. Any coexistent or subsequent hyperplasia of conventional type (World Health Organization classification) or adenocarcinoma was recorded. The age of patients ranged from 23 to 82 years (median, 53 y); 36 (61%) were postmenopausal. The majority presented with abnormal vaginal bleeding. Sixteen patients (27%) were receiving hormonal preparations including 5 who were treated with a progestogen for preexisting endometrial hyperplasia or low-grade endometrioid adenocarcinoma. The histologic diagnosis of PPE was made in 49 biopsies and in 10 hysterectomy specimens. Thirty-six cases (61%) were classified as group 1 and 23 (39%) as group 2. In 47 cases (80%), there was a coexisting endometrial polyp, 39 (66%) of which were involved by the PPE. Fifty-three cases (90%) had coexisting epithelial metaplastic changes, 41 (77%) of which were involved by the PPE. The most common type of metaplasia was mucinous (41 of 59 cases, or 69%). Follow-up information was known for 46 patients (78%). Coexistent or subsequent nonatypical and atypical hyperplasia was found in 8 (17%) and 6 cases (13%), respectively. In 6 of the 46 cases (13%), a low-grade endometrioid adenocarcinoma was present either in the original specimen or during follow-up. In contrast to group 1 PPE, those with group 2 features were significantly associated with concurrent or subsequent premalignant lesions (nonatypical and atypical hyperplasia) or carcinoma (P<0.0001). This study indicates that localized and architecturally simple PPEs confined to a completely removed polyp are usually associated with a benign outcome and may be appropriately labeled as "benign papillary proliferation of the endometrium." Lesions with architecturally complex papillae, especially when extensive, have an increased risk of concurrent or subsequent endometrial hyperplasia and carcinoma and should probably be regarded as analogous to atypical complex hyperplasia, and the term "complex papillary hyperplasia" is appropriate. As the distinction between simple and complex PPE may be difficult in small endometrial aspirational samples, consideration for curettage should be given to ascertain whether the lesion has been completely removed.

Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

PubMed

Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

2006-01-01

The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

Sex steroids and human behavior: prenatal androgen exposure and sex-typical play behavior in children.

PubMed

Hines, Melissa

2003-12-01

Gonadal hormones, particularly androgens, direct certain aspects of brain development and exert permanent influences on sex-typical behavior in nonhuman mammals. Androgens also influence human behavioral development, with the most convincing evidence coming from studies of sex-typical play. Girls exposed to unusually high levels of androgens prenatally, because they have the genetic disorder, congenital adrenal hyperplasia (CAH), show increased preferences for toys and activities usually preferred by boys, and for male playmates, and decreased preferences for toys and activities usually preferred by girls. Normal variability in androgen prenatally also has been related to subsequent sex-typed play behavior in girls, and nonhuman primates have been observed to show sex-typed preferences for human toys. These findings suggest that androgen during early development influences childhood play behavior in humans at least in part by altering brain development.

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

PubMed

Sideri, Mario; Jones, Ronald W; Wilkinson, Edward J; Preti, Mario; Heller, Debra S; Scurry, James; Haefner, Hope; Neill, Sallie

2005-11-01

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

[Endometrial hyperplasia, diagnosis. Clinical, paraclinical exam and management].

PubMed

Pangal, Alexandra; Costăchescu, Gh; Aldea, Marie Jeanne

2010-01-01

Factors associated with unopposed estrogenic stimulation such as obesity, exogenous hormone use endometrial hyperplasia are related to the development of the most common form of endometrial carcinoma, that is, the endometroid subtype. We selected a group of patients diagnosed with endometrial hyperplasia by endometrial biopsy and histopathological examination. The main complaint in all cases was abnormal uterine bleeding. All patients had gynecological examination, vaginal ultrasound, hysteroscopy endometrial biopsy or D&C. 32 patients had also immunohistochemical staining for Ki67, EGF, ER, PGR. Cases with ages between 24-67 years were classified as: 100 simple hyperplasia, 10 complex hyperplasia, 43 atypical simple hyperplasia, 7 atypical complex hyperplasia. PR were 40-60% at all forms of hyperplasia, E2R were 30-40% in simple hyperplasia without atypia and 50-70% in complex hyperplasia without atypia. Correlation between immunohistochemical expression of E2R, PGR, Ki-67, EGF and body mass revealed an high immunohistochemical expression of E2R and Ki-67 in patients with hyperplasia without atypia and a low expression and high reactivity of EGF in cases with high body mass. Vaginal ultrasound and hysteroscopy are efficacious completion for histopathological diagnosis. We recommend an age/risk appropriate screening to detect risk factors and early disease in the asymptomatic patients.

Weight loss reduces breast ductal fluid estrogens in obese postmenopausal women: a single arm intervention pilot study.

PubMed

Carpenter, Catherine L; Duvall, Karen; Jardack, Patricia; Li, Luyi; Henning, Susanne M; Li, Zhaoping; Heber, David

2012-12-05

Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women. We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2) postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass); exercise fitness (maximum oxygen consumption (VO2Max); 1-repetition strength maximum); and breast ductal lavage. Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop), VO2Max (+36% increase) and strength improvement (+26%). Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline), estrone sulfate (-10%), estradiol (-25%), and Il-6 (-33%). Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast: friends or foes?

PubMed

Agahozo, Marie Colombe; Hammerl, Dora; Debets, Reno; Kok, Marleen; van Deurzen, Carolien H M

2018-02-20

In the past three decades, the detection rate of ductal carcinoma in situ of the breast has dramatically increased due to breast screening programs. As a consequence, about 20% of all breast cancer cases are detected in this early in situ stage. Some ductal carcinoma in situ cases will progress to invasive breast cancer, while other cases are likely to have an indolent biological behavior. The presence of tumor-infiltrating lymphocytes is seen as a promising prognostic and predictive marker in invasive breast cancer, mainly in HER2-positive and triple-negative subtypes. Here, we summarize the current understanding regarding immune infiltrates in invasive breast cancer and highlight recent observations regarding the presence and potential clinical significance of such immune infiltrates in patients with ductal carcinoma in situ. The presence of tumor-infiltrating lymphocytes, their numbers, composition, and potential relationship with genomic status will be discussed. Finally, we propose that a combination of genetic and immune markers may better stratify ductal carcinoma in situ subtypes with respect to tumor evolution.

[Modern tendencies in treatment of atypical glandular hyperplasia--our and foreign experience].

PubMed

Ivanov, S; Kovachev, E; Tsonev, A; Abbud, A

2010-01-01

Our aim was to summarize our and foreign experience in the field of diagnosis, progression and modern treatment of precancer of the endometrium-the atypical glandular hyperplasia. We researched 750 cases with glandular and atypical glandular hyperplasia for 10 years period (2000-2010). The hyperplasia were followed up for progression from glandular hyperplasia into atypical glandular hyperplasia and early endometrial cancer. The hyperplasias were evaluated with or without progestagen hormonal therapy. All patients were treated by D&C before and after the hormonal treatment. The main symptom in all patients was the postmenopausal bleeding (72% from the cases). In 90% of the patients (675) there was obesity. Exogenous use of estrogens was found in 30% (225) of the patients. The cases with complex hyperplasia in 12% (65/525) progressed into atypical glandular hyperplasia and in 4% (21/525) progressed into endometrial cancer. The patients with atypical glandular hyperplasia in 60% (90/150) progressed into endometrial cancer. Remission was observed in 70% of the patients (194/278) with glandular hyperplasia and progestagen treatment. The remission was detected by the golden standart (D&C). The patients without hormonal treatment and with complex glandular hyperplasia have in 15% (37/247) remission. Except with progestagen therapy, we have also 15 patients treated with GnRh-analogs (Zoladex a 3.6 mg) for 3-6 months. For them we have 80% (12/15) remission. The glandular hyperplasia without atypical cells can be influenced by the hormonal treatment with progestagens and GnRh-analogs. Nevertheless this hormonal treatment--before and after we have to perform D&C and to follow up patients by ultrasound measuring the endometrial thickness. If the fertility plans of the patients are over and if they are in postmenopause with histological result from D&C-atypical glandular hyperplasia--we have to treat them more radically with simple total hysterectomy.

Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation.

PubMed

Mneimneh, Wadad S; Gökmen-Polar, Yesim; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

2015-11-01

We report nine cases of micronodular thymoma with lymphoid B-cell hyperplasia and one case of micronodular thymic carcinoma with lymphoid hyperplasia from our institution. For a better understanding of these rare tumors, clinical records, and histological features of these cases were reviewed, with detailed review of additional 64 literature cases of micronodular thymic neoplasms. The joint analysis identified 64 cases of micronodular thymoma with lymphoid B-cell hyperplasia and 9 cases of micronodular thymic carcinoma with lymphoid hyperplasia. Both groups revealed slight male predilection, with male:female ratio of 1.3:1 and 5:4, and occurred at >40 years of age, with a mean of 64 (41-83) and 62 (42-78) years, respectively. Myasthenia gravis was noted in 3/64 (5%) and 1/9 (11%) patients, respectively. Other systemic, disimmune, or hematologic disorders were noted in 6/64 (9%) and 1/9 (11%) patients, respectively. Components of conventional thymoma were reported in 11/64 (17%) micronodular thymomas with lymphoid B-cell hyperplasia, with transitional morphology between the two components in most of them. Cellular morphology was predominantly spindle in micronodular thymoma with lymphoid B-cell hyperplasia when specified (30/43), and epithelioid in micronodular thymic carcinoma with lymphoid hyperplasia (6/9), and cytological atypia was more encountered in the latter. Dedifferentiation/transformation from micronodular thymoma with lymphoid B-cell hyperplasia to micronodular thymic carcinoma with lymphoid hyperplasia seems to occur in a small subset of cases. Three cases of micronodular thymomas with lymphoid B-cell hyperplasia were described with co-existent low-grade B-cell lymphomas. Follow-up data were available for 30 micronodular thymomas with lymphoid B-cell hyperplasia and 6 micronodular thymic carcinomas with lymphoid hyperplasia, with a mean of 47 (0.2-180) months and 23 (3-39) months, respectively. Patients were alive without disease, except for five micronodular thymoma with lymphoid B-cell hyperplasia patients (dead from unrelated causes), and one micronodular thymic carcinoma with lymphoid hyperplasia patient (dead of disease).

Development of a Vaccine Targeting Triple-Negative Breast Cancer

DTIC Science & Technology

2013-11-01

node Mild hyperplasia and moderate granulomatous perinodal cellulitis mild hyperplasia mild hyperplasia and granulomatous lymphadenitis with...free lipid NSL Mild hyperplasia and moderate granulomatous perinodal cellulitis and steatosis, chronic. Salivary glands NSL NSL NSL NSL NSL

Review of the national external quality assessment (EQA) scheme for breast pathology in the UK.

PubMed

Rakha, Emad A; Bennett, Rachel L; Coleman, Derek; Pinder, Sarah E; Ellis, Ian O

2017-01-01

The National Health Service Breast Screening Programme (NHSBSP; pathology) external quality assurance (EQA) scheme aims to provide a mechanism for examination and monitoring of concordance of pathology reporting within the UK. This study aims to review the breast EQA scheme performance data collected over a 24-year period following its introduction. Data on circulations, number of cases and diagnosis were collected. Detailed analyses with and without combinations of certain diagnostic entities, and over different time periods were performed. Overall, of 576 cases (172 benign, 11 atypical hyperplasia, 98 ductal carcinoma in situ/microinvasive and 295 invasive disease), consistency of assessment of diagnostic parameters was very high (overall k=0.80; k for benign diagnosis=0.79; k for invasive disease=0.91). For distinguishing benign versus malignant lesions, no further improvement is considered possible in view of the limitations of the scheme methodology. Although diagnostic consistency of atypical hyperplasia remains at a low level, combining it with the benign category results in a high level of agreement (k=0.93). The level of consistency of reporting prognostic information is variable and some items such as lymphovascular invasion and tumour size measurement may need further intervention to improve their reporting consistency. Although the level of consistency of reporting of histological grade remained at a moderate level overall (k=0.48), it was variable among cases and appears to have levelled off; no further significant improvement is expected and no significant impact of the previous publication of guidelines is observed. These results provide further evidence to indicate the value of the breast EQA scheme in monitoring performance and the identification of specific areas where improvement or new approaches are required. For most parameters, the concordance of reporting reached a plateaux a few years after the introduction of the EQA scheme. It is important to maintain this high level and also to tackle specific low-performance areas innovatively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prostatic arterial embolization: post-procedural follow-up.

PubMed

Fernandes, Lucia; Rio Tinto, Hugo; Pereira, Jose; Duarte, Marisa; Bilhim, Tiago; Martins Pisco, João

2012-12-01

Prostatic arterial embolization (PAE) gained special attention in the past years as a potential minimally invasive technique for benign prostatic hyperplasia. Treatment decisions are based on morbidity and quality-of-life issues and the patient has a central role in decision-making. Medical therapy is a first-line treatment option and surgery is usually performed to improve symptoms and decrease the progression of disease in patients who develop complications or who have inadequately controlled symptoms on medical treatment. The use of validated questionnaires to assess disease severity and sexual function, uroflowmetry studies, prostate-specific antigen and prostate volume measurements are essential when evaluating patients before PAE and to evaluate response to treatment. PAE may be performed safely with minimal morbidity and without associated mortality. The minimally invasive nature of the technique inducing a significant improvement in symptom severity associated with prostate volume reduction and a slight improvement in the sexual function are major advantages. However, as with other surgical therapies for benign prostatic hyperplasia, up to 15% of patients fail to show improvement significantly after PAE, and there is a modest improvement of the peak urinary flow. Copyright © 2012 Elsevier Inc. All rights reserved.

Inhibition of AMPK and Krebs cycle gene expression drives metabolic remodeling of Pten-deficient preneoplastic thyroid cells.

PubMed

Antico Arciuch, Valeria G; Russo, Marika A; Kang, Kristy S; Di Cristofano, Antonio

2013-09-01

Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators. ©2013 AACR.

[The imaging diagnosis of hepatic focal nodular hyperplasia].

PubMed

Bazzocchi, M; Macorig, D; Cecconi, P; Gozzi, G

1991-12-01

Focal nodular hyperplasia (FNH) is a rare benign hepatocellular tumor occurring in noncirrhotic patients, mostly females, 20-50 years of age. It is usually asymptomatic. The authors took the lead from 5 cases of FNH studied over last year to analyze the different patterns exhibited by the condition on the various imaging techniques currently available. At scintigraphy with 99mTc DISIDA or with TcSC, FNH can be hyper, normal, or hypocaptating. On US scans, the lesion is often homogeneous and isoechoic, but it can also be hyper/hypoechoic. With Doppler US, high-flow signals can be observed. On unenhanced CT scans the lesion is solid, well-demarcated, isodense or slightly hyperdense; sometimes it shows a central hypodense area corresponding to fibrovascular scar. On postcontrast scans it appears hyper/isodense. At dynamic CT the lesion density, which is high during the arterial phase, decreases quickly in the parenchymal and the venous phases and reaches equal/inferior values to surrounding liver parenchyma. On liver angio-CT it is sometimes possible to visualize the bile ducts in the central scar. At angiography, FNH is hypervascular and homogeneous. On MR scans, in T1-weighted SE sequences, the condition is isointense or slightly hypointense, whereas on T2-weighted pulse sequences it is slightly hyperintense; the central scar is hypointense on T1, and hyperintense on T2, weighted scans. As we have no pathognomonic patterns but only orientative ones, a reliable differential diagnosis with hepatocellular adenoma (HA) and fibrolamellar hepatocellular carcinoma (FL-HCC) must be based on biopsy or cytology or, even better, histology. The differential diagnosis is nevertheless necessary because, while FNH does not usually require a surgical approach but only a radiological follow-up, both HA (due to possible bleeding and degeneration) and FL-HCC require surgery.

[Pathological and immunohistochemical analysis of giant cells of pancreas].

PubMed

Miyake, T; Suda, K; Yamamura, A; Tada, Y

1997-10-01

Multinucleated giant cells in the pancreas (five giant cell carcinomas, a mucinous cystadenocarcinoma attended with many osteoclast-like giant cells, 42 invasive ductal carcinomas and 29 chronic pancreatitises) were examined. Three types of multinucleated giant cell were identified: epithelial type, coexpressive type, mesenchymal type. Epithelial type expressed epithelial markers, such as keratin and EMA in 23 ductal carcinomas. Coexpressive type expressed both epithelial markers and mesenchymal marker vimentin was in four ductal carcinomas. Mesenchymal type expressed mesenchymal markers, vimentin and CD68 in four osteoclastoid type giant cell carcinomas, the mucinous cystadenocarcinoma, six ductal carcinomas and ten chronic pancreatitises. Epithelial and coexpressive type were considered to be epithelial neoplastic origin, those had bizarre appearance and transitional area from definite adenocarcinoma area. Vimentin expression is associated with sarcomatous proliferation. Mesenchymal type was considered to be nonneoplastic and a certain type of macrophage polykaryons.

Inverted ductal papilloma of the oral cavity secondary to lower lip trauma. A case report and literature review

PubMed Central

Sala-Pérez, Sergi; España-Tost, Antoni; Vidal-Bel, August

2013-01-01

Inverted ductal papilloma of the oral cavity is an infrequent benign neoplasm of papillary appearance that originates in the secretory duct of a salivary gland. The etiology is unknown, though some authors have related it to human papillomavirus (HPV) infection. We present the case of a 40-year-old woman with a tumor of the lower lip mucosa. Histopathological study of the lesion diagnosed inverted ductal papilloma of the oral cavity. Human papillomavirus DNA detection and typing based on tumor lesion DNA amplification and posterior hybridization, revealed no presence of viral DNA. The antecedents of trauma reported by the patient could have played an important role in the development of this tumor. Key words:Inverted ductal papilloma, intraductal papilloma, oral papilloma, papillary epidermoid adenoma. PMID:24455058

Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

PubMed

Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

2018-06-06

Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis

PubMed Central

Reichert, Maximilian; Takano, Shigetsugu; von Burstin, Johannes; Kim, Sang-Bae; Lee, Ju-Seog; Ihida-Stansbury, Kaori; Hahn, Christopher; Heeg, Steffen; Schneider, Günter; Rhim, Andrew D.; Stanger, Ben Z.; Rustgi, Anil K.

2013-01-01

Pancreatic exocrine cell plasticity can be observed during development, pancreatitis with subsequent regeneration, and also transformation. For example, acinar–ductal metaplasia (ADM) occurs during acute pancreatitis and might be viewed as a prelude to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) development. To elucidate regulatory processes that overlap ductal development, ADM, and the progression of normal cells to PanIN lesions, we undertook a systematic approach to identify the Prrx1 paired homeodomain Prrx1 transcriptional factor as a highly regulated gene in these processes. Prrx1 annotates a subset of pancreatic ductal epithelial cells in Prrx1creERT2-IRES-GFP mice. Furthermore, sorted Prrx1+ cells have the capacity to self-renew and expand during chronic pancreatitis. The two isoforms, Prrx1a and Prrx1b, regulate migration and invasion, respectively, in pancreatic cancer cells. In addition, Prrx1b is enriched in circulating pancreatic cells (Pdx1cre;LSL-KrasG12D/+;p53fl/+;R26YFP). Intriguingly, the Prrx1b isoform, which is also induced in ADM, binds the Sox9 promoter and positively regulates Sox9 expression. This suggests a new hierarchical scheme whereby a Prrx1–Sox9 axis may influence the emergence of acinar–ductal metaplasia and regeneration. Furthermore, our data provide a possible explanation of why pancreatic cancer is skewed toward a ductal fate. PMID:23355395

IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

PubMed

Zhao, Huan-Yu; Han, Yang; Wang, Jian; Yang, Lian-He; Zheng, Xiao-Ying; Du, Jiang; Wu, Guang-Ping; Wang, En-Hua

2017-06-01

IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

PubMed Central

Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

2015-01-01

Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with atypical endometrial hyperplasia. PMID:26623410

Florid reactive lymphoid hyperplasia of terminal ileum.

PubMed

Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

2010-01-01

Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn's disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn's disease. In florid lymphoid hyperplasia limited resection may be curative.

Direct growth-inhibitory effects of prostaglandin E2 in pancreatic cancer cells in vitro through an EP4/PKA-mediated mechanism.

PubMed

Schmidt, Andrea; Sinnett-Smith, James; Young, Steven; Chang, Hui-Hua; Hines, O Joe; Dawson, David W; Rozengurt, Enrique; Eibl, Guido

2017-06-01

There is strong evidence linking inflammation and the development of pancreatic ductal adenocarcinoma. Cyclooxygenase-2 (COX-2) and COX-2-derived PGE 2 are overexpressed in human and murine pancreatic ductal adenocarcinoma. Several studies have demonstrated an important role of COX-2-derived PGE 2 in tumor-stroma interactions; however, the direct growth effects of prostaglandin E 2 (PGE 2 ) on pancreatic ductal adenocarcinoma cells is less well defined. Our aim was to investigate the effects of PGE 2 on pancreatic ductal adenocarcinoma cell growth and to characterize the underlying mechanisms. Human pancreatic ductal adenocarcinoma cell lines, Panc-1 and MIA PaCa-2, were treated with PGE 2 in varying doses (0-10 μM). Effects on the phosphorylation of ERK1/2 were evaluated by Western blot. Colony formation was observed for cells treated with PGE 2 for 11 days. DNA synthesis was determined by (3H)-thymidine incorporation assay. Gene expression of E-type prostaglandin (EP)2/EP4 receptors and their correlation with survival in patients with pancreatic ductal adenocarcinoma were assessed using the RNA-Seq data set from The Cancer Genome Atlas Research Network. PGE 2 decreased the size and number of colonies in Panc-1 but not MIA PaCa-2 cells. In the Panc-1 cells, PGE 2 activated PKA/CREB and decreased phosphorylation of ERK1/2, which was reversed by an EP4 receptor antagonist, while an EP2 receptor antagonist had no effect. In contrast, in MIA PaCa-2 cells, PGE 2 had no effect on ERK1/2 phosphorylation. Treatment of both Panc-1 and MIA PaCa-2 cells with forskolin/IBMX decreased ERK1/2 phosphorylation. Finally, PGE 2 decreased DNA synthesis only in Panc-1 cells, which was reversed by an EP4 receptor antagonist. In human pancreatic ductal adenocarcinoma, high EP2 and low EP4 gene expression was correlated to worse median overall survival (15.6 vs 20.8 months, log-rank P = .017). Our study provides evidence that PGE 2 can inhibit directly pancreatic ductal adenocarcinoma cell growth through an EP4-mediated mechanism. Together with our gene expression and survival analysis, this observation suggests a protective role of EP4 receptors in human pancreatic ductal adenocarcinoma that expresses E-type prostaglandin receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Two Cases of Tuberous Sclerosis Complex Suggestive of Complicating Multifocal Micronodular Pneumocyte Hyperplasia: A Case Report.

PubMed

Nishida, Chinatsu; Yatera, Kazuhiro; Kido, Takashi; Noguchi, Shingo; Akata, Kentaro; Hanaka, Minako; Yamasaki, Kei; Hoshino, Teppei; Shimono, Masayuki; Ishimoto, Hiroshi; Sakamoto, Noriho; Mukae, Hiroshi

Multifocal micronodular pneumocyte hyperplasia (MMPH) is pathologically characterized by multifocal nodular hyperplasia of type Ⅱ pneumocyte-like cells. MMPH is usually complicated with tuberous sclerosis complex (TSC). MMPH patients tend to be asymptomatic or only slightly symptomatic. MMPH tends to progress slowly and needs no treatment. We herein describe two cases of MMPH with its characteristic radiological features and clinical manifestations of TSC. Case 1: a 20-year-old female with definitive TSC in infancy. Chest CT at the age of 18 revealed multiple nodular opacities and ground-glass attenuations in a scattered and random distribution in the bilateral lungs. Case 2: a 44-year-old female with probable TSC at 36 years of age. Chest CT at the age of 43 showed random areas of small ground-glass attenuations, predominantly in the upper lung fields. Case 1 and Case 2 have had no respiratory symptoms or radiographic changes in the recent two years and four years, respectively. Although pathological examinations of the lung were not performed because consent for surgical lung biospies was unobtainable, we considered that these pulmonary manifestations were most likely MMPH with TSC because of these characteristic radiographical findings of multiple nodular opacities and ground-glass attenuations of 10 mm or less in size and their scattered distribution, and because there have been no abnormal laboratory data or changes in their chest radiological findings for years. Neither patient is under treatment for pulmonary lesions. Although MMPH is a rare disease, multiple nodules and ground-glass attenuations on lung imaging findings should be considered as pulmonary manifestations in patients with TSC.

Florid reactive lymphoid hyperplasia of terminal ileum

PubMed Central

Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

2010-01-01

Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may be curative. PMID:22242075

Development of an animal model of fibrous cholangitis in pigs.

PubMed

Lainakis, Nektarios G; Papalois, Apostolos; Agrogiannis, Georgios; Antonopoulos, Constantine N; Michail, Panagiotis; Bastounis, Elias; Patsouris, Efstathios; Felekouras, Evangelos

2014-04-01

The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0-5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Statistically significant differences were observed for most of the histopathological markers between the group of pigs' offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas.

PubMed

Trulsson, Lena M; Gasslander, Thomas; Sundqvist, Tommy; Svanvik, Joar

2002-06-15

Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by N(omega)-nitro-L-arginine (L-NNA) reduced the urinary excretion of NO(2)/NO(3) and raised serum L-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO(2)/NO(3). The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, L-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of L-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.

Ductal carcinoma in situ (DCIS) of the breast: the need for psychosocial research.

PubMed

Carrera, C; Payne, S

1999-01-01

Since the introduction of the National Health Service Breast Screening Programme (NHSBSP), the number of ductal carcinoma in situ (DCIS) cases has increased considerably. Despite its increased incidence, some NHS leaflets and reports do not mention it, and the general public seems largely unaware of its existence. There are numerous biological studies dealing with this condition, but its psychosocial aspects seem to have been neglected. We have only been able to locate two British studies (Farmer, A. 1996. Unpublished PhD thesis, University of Southampton; Webb, C. and Koch, T. 1997. J. Adv. Nurs., 25, 154-525) that address some of the psychosocial issues associated with DCIS. This paper starts by defining DCIS and explaining its usual presentation, natural history and epidemiology. The treatment options for DCIS are described, together with the great deal of confusion and lack of agreement that accompanies them. The psychological issues that women with screen-detected DCIS have to deal with are different from those affecting women diagnosed with symptomatic breast cancer, and a summary of these issues is given. Finally, some suggestions for future psychosocial research are provided. Because the UK as a whole was not covered by the NHSBSP until 1990 (Baum, M. 1995. Lancet, 346, 436; Gage and Fouquet, 1997), the main focus will be on papers published from that year onwards, although some key papers published before then will also be included. The papers reviewed here were found in MEDLINE, EMBASE and BIDS (ISI). Copyright 1999 John Wiley & Sons, Ltd.

Peripheral ossifying fibroma of oral cavity: histopathologic differential diagnoses.

PubMed

Shamim, Thorakkal

2012-01-01

Peripheral ossifying fibroma is a benign neoplasm that usuallydevelops from gingiva, presenting as an exophytic smooth surfaced pink or red nodular mass that is sessile or is less frequently seen on a pedicle. From the Indian perspective, it is usually noticed in 5th-6th decades of life with female predilection. Microscopically, the tumour shows stratified squamous epithelium and highly cellular fibrous stroma, sparse endothelial proliferation with fibroblasts and dystrophic calcifications. It has to be differentiated histopathologically from pyogenic granuloma, fibroma, peripheral giant cell granuloma, peripheral odontogenic fibroma and fibrous hyperplasia. A case of peripheral ossifying fibroma of maxillary gingiva in a 55-year-old Indian woman is reported.

[Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

PubMed

Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

2015-03-01

Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

ClinicalTrials.gov

2017-09-25

Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

Bilateral extensive ductitis obliterans manifested by bloody nipple discharge in a patient with long-term diabetes mellitus.

PubMed

Wang, Zhiqin; Leonard, Morton H; Khamapirad, Tuenchit; Castro, Claudia Y

2007-01-01

Ductitis obliterans or mastitis obliterans is a rare late manifestation of mammary ductal ectasia. We describe a long-term diabetic patient who presented with bilateral bloody nipple discharge and poorly defined nodularities around the nipple of both breasts. The ductography showed multiple segments of irregular ductal narrowing and intraluminal filling defects in both breasts. The bilateral resection of the sub-areolar portion of the breast showed exuberant fibrous obliteration of the large- and medium-sized ducts by granulation tissue associated with few histiocytes. Ductal dilatation and intraductal accumulation of histiocytes was also present. This represents a late and florid form of mammary ductal ectasia. Differential diagnostic considerations including fibrocystic changes, diabetic sclerosing lymphocytic lobulitis, idiopathic granulomatous lobular mastitis, and periductal mastitis (Zuska disease) are discussed. Accurate diagnosis can help avoid or limit radical surgeries in this group of patients.

Predictors of successful closure of patent ductus arteriosus with indomethacin.

PubMed

Ahamed, M F; Verma, P; Lee, S; Vega, M; Wang, D; Kim, M; Fuloria, M

2015-09-01

To determine whether platelet counts can predict the likelihood of successful closure of patent ductus arteriosus (PDA) with indomethacin. This was a retrospective cohort study of infants <32 weeks' gestational age (GA) and birth weight <1500 g with PDA. Clinical characteristics between infants who achieved ductal closure with indomethacin and those who failed were compared. Multivariable logistic regression was used to identify predictors of successful ductal closure. In infants with hemodynamically significant PDA, older GA (odds ratio=1.54; 95% confidence interval: 1.12 to 2.13), male gender (odds ratio=3.02; 95% confidence interval: 1.08 to 8.49) and higher platelet count (odds ratio=1.5; 95% confidence interval: 1.04 to 2.17) prior to indomethacin treatment were associated with successful ductal closure with indomethacin. Older GA, male gender and higher platelet count at time of treatment of hemodynamically significant PDA are predictors of successful ductal closure with indomethacin.

[Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution].

PubMed

Rubio-Puchol, O; Garzón-Pastor, S; Salom-Vendrell, C; Hernández-Mijares, A

Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis.

PubMed

Nealon, William H; Bhutani, Manoop; Riall, Taylor S; Raju, Gottumukkala; Ozkan, Orhan; Neilan, Ryan

2009-05-01

Precepts about acute pancreatitis, necrotizing pancreatitis, and pancreatic fluid collections or pseudocyst rarely include the impact of pancreatic ductal injuries on their natural course and outcomes. We previously examined and established a system to categorize ductal changes. We sought a unifying concept that may predict course and direct therapies in these complex patients. We use our system categorizing ductal changes in pseudocyst of the pancreas and severe necrotizing pancreatitis (type I, normal duct; type II, duct stricture; type III, duct occlusion or "disconnected duct"; and type IV, chronic pancreatitis). From 1985 to 2006, a policy was implemented of routine imaging (cross-sectional, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography). Clinical outcomes were measured. Among 563 patients with pseudocyst, 142 resolved spontaneously (87% of type I, 5% of type II, and no type III, and 3% of type IV). Percutaneous drainage was successful in 83% of type I, 49% of type II, and no type III or type IV. Among 174 patients with severe acute pancreatitis percutaneous drainage was successful in 64% of type I, 38% of type II, and no type III. Operative debridement was required in 39% of type I and 83% and 85% of types II and III, respectively. Persistent fistula after debridement occurred in 27%, 54%, and 85% of types I, II, and III ducts, respectively. Late complications correlated with duct injury. Pancreatic ductal changes predict spontaneous resolution, success of nonoperative measures, and direct therapies in pseudocyst. Ductal changes also predict patients with necrotizing pancreatitis who are most likely to have immediate and delayed complications.

Metastatic prostate adenocarcinoma to the penis: a series of 29 cases with predilection for ductal adenocarcinoma.

PubMed

Ellis, Carla L; Epstein, Jonathan I

2015-01-01

Twenty-nine men with metastatic prostate adenocarcinoma to the penis were identified at our institution between 1993 and 2013. Of the 29 patients, 19 had a prior history of adenocarcinoma of the prostate, and 8 of those had ductal features in the primary lesion. Sixteen of 29 revealed ductal features in the metastasis. Seven of the 8 cases with ductal features in the primary had ductal features in the penile metastasis. Seven penile metastases were proven to be of prostatic origin solely by immunohistochemistry. Three cases were originally misdiagnosed as urothelial carcinoma upon review of the penile lesion. Other variant morphologies in the metastases included sarcomatoid carcinoma, small cell carcinoma, and adenosquamous carcinoma. In summary, prostate carcinoma involving the penis displays ductal features considerably more often than prostate cancer in general. Features that can cause difficulty in recognizing metastatic prostate adenocarcinoma to the penis include the unusual anatomic site for prostate cancer, poor differentiation, an increased prevalence of variant morphology, a long interval from the primary lesion, and, in some cases, no documented history of a primary prostatic lesion. Immunohistochemical analysis should be performed to rule out prostate carcinoma in penile/penile urethral tumors with morphology that differs from typical squamous or urothelial carcinoma. Even in the setting of metastatic disease, there is a critical need for an accurate diagnosis so that the appropriate therapy can be initiated, symptomatic relief can be provided, and long-term survival achieved in some cases, while at the same time avoiding penectomy for a misdiagnosis of a primary penile cancer.

[Toxoplasmosis in patients with lymphoid hyperplasia of the head and neck].

PubMed

Yariktaş, Murat; Demirci, Mustafa; Döner, Fehmi; Kaya, Selçuk; Doğru, Harun

2004-01-01

To investigate the incidence of toxoplasmosis in patients with lymphoid hyperplasia of the head and neck. In this study, 53 patients (32 males, 21 females; mean age 11.2+/-4.3 years, range 5 to 22) were investigated. There were hypertrophic tonsillitis in 13 patients, hypertrophic tonsillitis and adenoid hyperplasia in 22 patients, adenoid hyperplasia in 10 patients, and lymphadenopathy of the neck in eight patients. In venous blood samples, IgM and IgG antibodies for Toxoplasma gondii were investigated with the enzyme-linked immunoabsorbent assay (Axsym, Abbott). Positive IgG was determined in 23 patients (48%) with hypertrophic tonsillitis (n=6), hypertrophic tonsillitis and adenoid hyperplasia (n=10), adenoid hyperplasia (n=3), and lymphadenopathy of the neck (n=4). Positive IgM was determined in 5 patients (9.4%) with hypertrophic tonsillitis (n=1), hypertrophic tonsillitis and adenoid hyperplasia (n=1), and lymphadenopathy of the neck (n=3). Toxoplasmosis, which is known to cause lymphadenopathy, may be a reason for lymphadenopathy of the neck. Toxoplasmosis should be considered in the differential diagnosis of untreated patients with tonsillitis, adenoid hyperplasia, and chronic neck lymphadenopathy.

Broccoli Sprout Extract in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-04

Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Downstream anastomotic hyperplasia. A mechanism of failure in Dacron arterial grafts.

PubMed Central

LoGerfo, F W; Quist, W C; Nowak, M D; Crawshaw, H M; Haudenschild, C C

1983-01-01

The precise location and progression of anastomotic hyperplasia and its possible relationship to flow disturbances was investigated in femoro-femoral Dacron grafts in 28 dogs. In 13 grafts, the outflow from the end-to-side downstream anastomosis was bidirectional (BDO), and in 15 it was unidirectional (UDO) (distally). Grafts were electively removed at intervals of two to 196 days or at the time of thrombosis. Each anastomosis and adjacent artery was perfusion-fixed and sectioned sagittally. The mean sagittal section was projected onto a digitized pad, and the total area of hyperplasia internal to the arterial internal elastic lamina and within the adjacent graft was integrated by computer. The location of the hyperplasia was compared with previously established sites of flow separation and stagnation. The observation was made that hyperplasia is significantly greater at the downstream, as compared with the upstream, anastomosis in both groups (BDO = p less than 0.001 and UDO = p less than 0.001) (analysis of variance for independent groups). Furthermore, this downstream hyperplasia was progressive with time (BDO p less than 0.01) (UDO p less than 0.01); Spearman Rank Correlation. There was no significant increase in the extent of downstream hyperplasia where flow separation was known to be greater (BDO). Five grafts failed (three BDO, two UDO), as a result of complete occlusion of the downstream anastomosis by fibrous hyperplasia. Transmission electron microscopy showed the hyperplasia to consist of collagen-producing smooth muscle cells. Anastomotic hyperplasia is significantly greater at the downstream anastomosis, is progressive with time, and is the primary cause of failure of Dacron arterial grafts in this model. Quantitative analysis of downstream anastomotic hyperplasia may be a valuable measure of the biocompatibility of Dacron grafts. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6219641

Benign prostate hyperplasia (BPH) - resources

MedlinePlus

Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Institute of Diabetes and Digestive and Kidney ...

[Brunners gland hiperplasia. Report of two cases].

PubMed

Padilla Ruiz, Maykel

2014-04-01

Brunner's gland hyperplasia is an infrequent benign injury located on the first or second portion of the duodenum. The disease spectrum includes diffuse nodular hyperplasia, circumscribed nodular hyperplasia, and Brunner's gland adenoma. We report two cases, one with an adenoma of Brunner's glands as a duodenal polyp and the other as a diffuse nodular hyperplasia of the duodenal bulb.

Male ductal carcinoma in situ presenting as bloody nipple discharge: a case report and literature review.

PubMed

Simmons, Rache M

2002-01-01

Male breast carcinoma accounts for 1% of all diagnosed breast carcinoma. Pure ductal carcinoma in situ in men is extremely rare. Unfortunately, male breast cancer is often diagnosed at a late stage because of the minimal awareness of presenting symptoms by the patient and sometimes by the health care provider. Because of this late presentation, the overall prognosis is less favorable. This case is presented to emphasize the importance of recognizing bloody nipple discharge as a clinical sign of male ductal carcinoma in situ and an opportunity for early diagnosis.

A monte carlo study of restricted diffusion: Implications for diffusion MRI of prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-04-01

Diffusion MRI is used frequently to assess prostate cancer. The prostate consists of cellular tissue surrounding fluid filled ducts. Here, the diffusion properties of the ductal fluid alone were studied. Monte Carlo simulations were used to investigate ductal residence times to determine whether ducts can be regarded as forming a separate compartment and whether ductal radius could determine the Apparent Diffusion Coefficient (ADC) of the ductal fluid. Random walks were simulated in cavities. Average residence times were estimated for permeable cavities. Signal reductions resulting from application of a Stejskal-Tanner pulse sequence were calculated in impermeable cavities. Simulations were repeated for cavities of different radii and different diffusion times. Residence times are at least comparable with diffusion times even in relatively high grade tumors. ADCs asymptotically approach theoretical limiting values. At large radii and short diffusion times, ADCs are similar to free diffusion. At small radii and long diffusion times, ADCs are reduced toward zero, and kurtosis approaches a value of -1.2. Restricted diffusion in cavities of similar sizes to prostate ducts may reduce ductal ADCs. This may contribute to reductions in total ADC seen in prostate cancer. Magn Reson Med 77:1671-1677, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Lead poisoning in dogs: occurrence, source, clinical pathology, and electroencephalography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zook, B.C.; Carpenter, J.L.; Roberts, R.M.

1972-05-01

Accidental lead poisoning was diagnosed and studied in 236 dogs. The disease incidence increased annually after 1963 and was more common in Poodles and dogs less than 1 year old. The incidence was greatest in summer and early fall and was more common in dogs which dwelt in slum areas than was expected. Lead-based paints were the most frequent source of poisoning. Results of hematologic and urinary determinations supported those of previous studies. The diagnostic importance of nucleated and stippled red blood cells (RBC) in peripheral blood films was emphasized, and urine sediments frequently contained casts with few inflammatory cells.more » In addition, reticulocyte counts were usually increased and sedimentation rates and Coomb's test results were normal. Results of bone marrow studies indicated hyperplasia of, and partial maturation defect in, the erythrocytic series of most dogs. Determinations of various clinical chemistry tests and cerebrospinal fluid analysis were usually normal. Electroencephalographic changes consisted of irregular, generalized slow-wave activity of increased amplitude. 20 references, 5 figures, 12 tables.« less

Expression of cyclin D{sub 1} during endotoxin-induced aleveolar type II cell hyperplasia in rat lung and the detection of apoptotic cells during the remodeling process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tesfaigzi, J.; Wood, M.B.; Johnson, N.F.

Our studies have shown that endotoxin intratracheally instilled into the rat lung induces proliferation of alveolar type II cells. In that study, the alveolar type II cells. In that study, the alveolar type II cell hyperplasia occurred 2 d after instillation of endotoxin and persisted for a further 2 d. After hyperplasia, the lung remodeled and returned to a normal state within 24-48 h. Understanding the mechanisms involved in the remodeling process of this transient hyperplasia may be useful to identify molecular changes that are altered in neoplasia. The purpose of the present study was to corroborate induction of epithelialmore » cell hyperplasia by endotoxin and to delineate mechanisms involved in tissue remodeling after endotoxin-induced alveolar type II cell hyperplasia. In conclusion, immonostaining with cyclin D1 and cytokeratin shows that endotoxin induced epithelial cell proliferation and resulted in hyperplasia in the lung which persisted through 4 d post-instillation.« less

Extracellular Ca2+ Sensing in Salivary Ductal Cells*

PubMed Central

Bandyopadhyay, Bidhan C.; Swaim, William D.; Sarkar, Ankana; Liu, Xibao; Ambudkar, Indu S.

2012-01-01

Ca2+ is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na+ and Cl− get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca2+] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca2+ remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca2+ reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca2+] or by aromatic amino acid, l-phenylalanine (l-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca2+ influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca2+ entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca2+ sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca2+] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca2+]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis). PMID:22778254

[Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

PubMed

Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

2014-01-01

Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

Treatment and outcome of traumatic biliary injuries in children.

PubMed

Soukup, Elizabeth S; Russell, Katie W; Metzger, Ryan; Scaife, Eric R; Barnhart, Douglas C; Rollins, Michael D

2014-02-01

Traumatic biliary tract injuries in children are rare but may result in significant morbidity. The objective of this study was to review the occurrence of traumatic biliary tract injuries in children, management strategies, and outcome. We conducted a retrospective review of patients with biliary tract injury using the trauma registry at our level 1 pediatric trauma center from 2002-2012. Twelve out of 13,582 trauma patients were identified, representing 0.09% of all trauma patients. All were secondary to blunt trauma. Mean age was 9.7 years [range 4-15], and mean Injury Severity Score was 31 ± 14, with overall survival of 92%. Biliary injuries included major ductal injury (6), minor ductal injury with biloma (4), gallbladder injury (2), and intrahepatic ductal injury (1). Major ductal injuries were managed by endoscopic retrograde cholangiopancreatography (ERCP) and biliary stent (5) and Roux-en-Y hepaticojejunostomy (1). Associated gallbladder injury was managed by cholecystectomy. In addition, the associated biloma was managed with percutaneous drainage (7), laparoscopic drainage (2), or during laparotomy (3). Two patients with ductal injuries developed late strictures after initial management with ERCP and stent placement. One of the two patients ultimately required a left hepatectomy, and the other has been managed conservatively without evidence of cholangitis. Two patients required placement of additional drains and prolonged antibiotics for superinfection following biloma drainage. Biliary tract injuries are rare in children, and many are amenable to adjunctive therapy, including ERCP and biliary stent placement with or without placement of a peritoneal drain. Patients with a discrete ductal injury are at higher risk for stricture and require close follow up. Hepaticojejunostomy remains the definitive repair for large extrahepatic biliary tract injuries or transections. © 2014.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Evaluation of AgNORs in Oral Potentially Malignant Lesions.

PubMed

Tomazelli, Karin Berria; Modolo, Filipe; Rivero, Elena Riet Correa

2015-01-01

Oral squamous cell carcinoma (OSCC) is usually preceded by detectable mucosal changes, as leukoplakias and erythroplakia. Histologically, these lesions can range from hyperkeratosis and acanthosis to epithelial dysplasia and even OSCC. The aim of this study was to investigate the proliferative activity, using AgNORs quantification proteins, in low- and high-risk oral epithelial dysplasia, OSCC, and nondysplastic epithelium (inflammatory fibrous hyperplasia). The sample was divided into 4 groups: G1: 10 cases of inflammatory fibrous hyperplasia (IFH), G2: 11 cases of low-risk epithelial dysplasia (LD), G3: 10 cases of high-risk epithelial dysplasia (HD), and G4: 11 cases of OSCC. The quantitative analysis was performed using an image processing software in photomicrographs at 1000x magnification. The one-way ANOVA was used for comparison of the mean AgNORs counts between the study groups. The mean AgNORs count was significantly higher (P ≤ 0.01) in OSCC when compared to IFH and the LD; however, it was not statistically different from HD. The mean number of LD was significantly lower than the HD and OSCC, with no difference related to IFH. AgNORs quantification can be an important and cheap method to help in the determination of the degree of epithelial dysplasia and, consequently, in the analysis of their potential for malignant transformation.

Developmental pathway from leaves to galls induced by a sap-feeding insect on Schinus polygamus (Cav.) Cabrera (Anacardiaceae).

PubMed

Dias, Graciela G; Ferreira, Bruno G; Moreira, Gilson R P; Isaias, Rosy M S

2013-03-01

Galling sap-feeding insects are presumed to cause only minor changes in host plant tissues, because they usually do not require development of nutritive tissues for their own use. This premise was examined through comparison of the histometry, cytometry and anatomical development of non-galled leaves and galls of Calophya duvauae (Scott) (Hemiptera: Calophyidae) on Schinus polygamus (Cav.) Cabrera (Anacardiaceae). Cell fates changed from non-galled leaves to galls during the course of tissue differentiation. C. duvauae caused changes in dermal, ground, and vascular systems of the leaves of S. polygamus. Its feeding activity induced the homogenization of the parenchyma, and the neoformation of vascular bundles and trichomes. The histometric and cytometric data revealed compensatory effects of hyperplasia and cell hypertrophy in the epidermis, with hyperplasia predominating in the adaxial epidermis. There was a balance between these processes in the other tissues. Thus, we found major differences between the developmental pathways of non-galled leaves and galls. These changes were associated with phenotypic alterations related to shelter and appropriate microenvironmental conditions for the gall inducer. The nondifferentiation of a typical nutritive tissue in this case was compared to other non-phylogenetically related arthropod gall systems, and is suggested to result from convergence associated with the piercing feeding apparatus of the corresponding gall-inducer.

3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

ClinicalTrials.gov

2017-12-29

Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

PubMed Central

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-01-01

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001 PMID:24252877

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

PubMed

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-11-19

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

Imaging pancreatobiliary ductal system with optical coherence tomography: A review

PubMed Central

Mahmud, Mohammad S; May, Gray R; Kamal, Mohammad M; Khwaja, Ahmed S; Sun, Carry; Vitkin, Alex; Yang, Victor XD

2013-01-01

An accurate, noninvasive and cost-effective method of in situ tissue evaluation during endoscopy would be highly advantageous for the detection of dysplasia or early cancer and for identifying different disease stages. Optical coherence tomography (OCT) is a noninvasive, high-resolution (1-10 μm) emerging optical imaging method with potential for identifying microscopic subsurface features in the pancreatic and biliary ductal system. Tissue microstructure of pancreaticobiliary ductal system has been successfully imaged by inserting an OCT probe through a standard endoscope operative channel. High-resolution OCT images and the technique’s endoscopic compatibility have allowed for the microstructural diagnostic of the pancreatobiliary diseases. In this review, we discussed currently available pancreaticobiliary ductal imaging systems to assess the pancreatobiliary tissue microstructure and to evaluate varieties of pancreaticobiliary disorders and diseases. Results show that OCT can improve the quality of images of pancreatobiliary system during endoscopic retrograde cholangiopancheatography procedure, which may be important in distinguishing between the neoplastic and non-neoplastic lesions. PMID:24255746

Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

2015-02-01

The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

Quantitatively characterizing the microstructural features of breast ductal carcinoma tissues in different progression stages by Mueller matrix microscope.

PubMed

Dong, Yang; Qi, Ji; He, Honghui; He, Chao; Liu, Shaoxiong; Wu, Jian; Elson, Daniel S; Ma, Hui

2017-08-01

Polarization imaging has been recognized as a potentially powerful technique for probing the microstructural information and optical properties of complex biological specimens. Recently, we have reported a Mueller matrix microscope by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission-light microscope, and applied it to differentiate human liver and cervical cancerous tissues with fibrosis. In this paper, we apply the Mueller matrix microscope for quantitative detection of human breast ductal carcinoma samples at different stages. The Mueller matrix polar decomposition and transformation parameters of the breast ductal tissues in different regions and at different stages are calculated and analyzed. For more quantitative comparisons, several widely-used image texture feature parameters are also calculated to characterize the difference in the polarimetric images. The experimental results indicate that the Mueller matrix microscope and the polarization parameters can facilitate the quantitative detection of breast ductal carcinoma tissues at different stages.

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

PubMed Central

Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

2013-01-01

Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.

Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells.

PubMed

Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja

2015-12-02

Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1 diabetes. In addition, the capability for rapid adaptation to different cell types suggests that, on occasion, enterovirus strains with different pathogenetic properties may arise from less pathogenic ancestors. Copyright © 2015 Elsevier B.V. All rights reserved.

Changes in initial expenditures for benign prostatic hyperplasia evaluation in the Medicare population: a comparison to overall Medicare inflation.

PubMed

Bellinger, Adam S; Elliott, Sean P; Yang, Liu; Wei, John T; Saigal, Christopher S; Smith, Alexandria; Wilt, Timothy J; Strope, Seth A

2012-05-01

Benign prostatic hyperplasia creates significant expenses for the Medicare program. We determined expenditure trends for benign prostatic hyperplasia evaluative testing after urologist consultation and placed these trends in the context of overall Medicare expenditures. Using a 5% national sample of Medicare beneficiaries from 2000 to 2007 we developed a cohort of 40,253 with claims for new visits to urologists for diagnoses consistent with symptomatic benign prostatic hyperplasia. We assessed trends in initial inflation and geography adjusted expenditures within 12 months of diagnosis by evaluative test categories derived from the 2003 American Urological Association guideline on the management of benign prostatic hyperplasia. Using governmental reports on Medicare expenditure trends for benign prostatic hyperplasia we compared expenditures to overall and imaging specific Medicare expenditures. Comparisons were assessed by the Z-test and regression analysis for linear trends, as appropriate. Between 2000 and 2007 inflation adjusted total Medicare expenditures per patient for the initial evaluation of patients with benign prostatic hyperplasia seen by urologists increased from $255.44 to $343.98 (p <0.0001). Benign prostatic hyperplasia related imaging increases were significantly less than overall Medicare imaging expenditure increases (55% vs 104%, p <0.001). The increase in per patient expenditures for benign prostatic hyperplasia was significantly lower than the increase in overall Medicare expenditures per enrollee (35% vs 45%, p = 0.0015). From 2000 to 2007 inflation adjusted expenditures increased for benign prostatic hyperplasia related evaluations. This growth was slower than the overall growth in Medicare expenditures. The increase in BPH related imaging expenditures was restrained compared to that of the Medicare program as a whole. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model.

PubMed

Hata, Junya; Satoh, Yuichi; Akaihata, Hidenori; Hiraki, Hiroyuki; Ogawa, Soichiro; Haga, Nobuhiro; Ishibashi, Kei; Aikawa, Ken; Kojima, Yoshiyuki

2016-07-01

To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model. Fetal urogenital sinus isolated from 20-day-old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time-dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole-genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation). Microarray analyses showed 926 upregulated (>2-fold change, P < 0.01) and 3217 downregulated genes (<0.5-fold change, P < 0.01) in benign prostatic hyperplasia specimens compared with normal prostate. Gene ontology analyses of upregulated genes showed predominant genetic themes of involvement in development (162 genes, P = 2.01 × 10(-4) ), response to stimulus (163 genes, P = 7.37 × 10(-13) ) and growth (32 genes, P = 1.93 × 10(-5) ). When we used both normal prostate and non-transplanted urogenital sinuses as controls to identify benign prostatic hyperplasia-specific genes, 507 and 406 genes were upregulated and downregulated, respectively. Functional network and pathway analyses showed that genes associated with apoptosis modulation by heat shock protein 70, interleukin-1, interleukin-2 and interleukin-5 signaling pathways, KIT signaling pathway, and secretin-like G-protein-coupled receptors, class B, were relatively activated during the growth process in the benign prostatic hyperplasia specimens. In contrast, genes associated with cholesterol biosynthesis were relatively inactivated. Our microarray analyses of the benign prostatic hyperplasia model rat might aid in clarifying the molecular mechanism of benign prostatic hyperplasia progression, and identifying molecular targets for benign prostatic hyperplasia treatment. © 2016 The Japanese Urological Association.

A Duodenal Ulcer Caused by Pancreatic Ductal Hypertension with Chronic Pancreatitis.

PubMed

Imoto, Akira; Masuda, Daisuke; Okuda, Atsushi; Takagi, Wataru; Onda, Saori; Sano, Tatsushi; Mikami, Takashi; Mohamed, Malak; Ogura, Takeshi; Higuchi, Kazuhide

2015-01-01

We herein describe the case of a 67-year-old woman with a duodenal ulcer thought to be caused by elevated pancreatic ductal pressure. The patient complained of continuous upper abdominal pain. Her medical history included idiopathic chronic pancreatitis. Endoscopy revealed a huge duodenal ulcer located on the inferior duodenal angle, which had not been seen on endoscopic retrograde pancreatography two months previously. A combination study using endoscopy and contrast imaging confirmed the relationship between the duodenal ulcer and the pancreatic branch duct. To our knowledge, this is the first case of duodenal ulcer thought to be caused by elevated pancreatic ductal pressure.

The intraductal approach to the breast: raison d'être

PubMed Central

King, Bonnie L; Love, Susan M

2006-01-01

Opportunities for the detection, prediction, and treatment of breast cancer exist at three biological levels: systemically via the blood, at the whole organ level, and within the individual ductal lobular structures of the breast. This review covers the evaluation of approaches targeted to the ductal lobular units, where breast cancer begins. Studies to date suggest the presence of 5 to 12 independent ductal lobular systems per breast, each harboring complex cellular fluids contributed by local and systemic processes. New techniques for accessing and interrogating these systems offer the potential to gauge the microenvironment of the breast and distill biological risk profiles. PMID:16677416

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

PubMed Central

2014-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients. Results In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2. Conclusions We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment. PMID:25560450

Juvenile Papillomatosis of the Breast in a Pre-Pubertal Girl: An Uncommon Diagnosis.

PubMed

Kafadar, Mehmet Tolga; Anadolulu, Zeynep; Anadolulu, Ali İhsan; Tarini, Emine Zeynep

2018-01-01

Juvenile papillomatosis of the breast represents a rare benign proliferative disorder that affects women younger than thirty years of age. Although it is a localized lesion, it does not have well-demarcated margins. These patients tend to have a strong family history for cancer. As it has similar clinical presentation with that of a fibroadenoma, it usually receives the diagnosis of the latter in the preoperative period. Nonetheless, it has distinct microscopic features such as ductal papillomatosis and cysts that are helpful in the diagnosis. In this article, a case of juvenile papillomatosis diagnosed in a young girl who presented due to a mass of the breast was presented. For the fairly rare case, a total mass excision was performed with preserved breast tissue. The exact diagnosis was made by postoperative histopathological examination.

Early detection, aggressive therapy: optimizing the management of feline mammary masses.

PubMed

Giménez, Fernanda; Hecht, Silke; Craig, Linden E; Legendre, Alfred M

2010-03-01

This article reviews the incidence, etiology, diagnosis, treatment and prognosis of mammary tumors in cats. Approximately 80% of feline mammary masses are malignant, with adenocarcinoma being the most common tumor type. Early diagnosis is, therefore, essential to improve the prognosis and quality of life of affected cats. Surgery is the most widely used treatment for malignant tumors. However, as mammary tumors are often advanced and metastasis has already occurred by the time of diagnosis, surgery routinely does not provide a cure. Ovariohysterectomy or hormonal therapy are the treatments of choice for fibroadenomatous hyperplasia (the most common benign mass) and usually lead to a successful outcome. Copyright 2010. Published by Elsevier Ltd.

NOGGIN IS REQUIRED FOR NORMAL LOBE PATTERNING AND DUCTAL BUDDING IN THE MOUSE PROSTATE

PubMed Central

Cook, Crist; Vezina, Chad M.; Hicks, Sarah M.; Shaw, Aubie; Yu, Min; Peterson, Richard E.; Bushman, Wade

2008-01-01

Mesenchymal expression of the BMP antagonist NOGGIN during prostate development plays a critical role in pre-natal ventral prostate development and opposes BMP4-mediated inhibition of cell proliferation during postnatal ductal development. Morphologic examination of newborn Noggin-/- male fetuses revealed genitourinary anomalies including cryptorchidism, incomplete separation of the hindgut from the urogenital sinus (UGS), absence of the ventral mesenchymal pad and a complete loss of ventral prostate (VP) budding. Examination of lobe-specific marker expression in the E14 Noggin-/- UGS rescued by transplantation under the renal capsule of a male nude mouse confirmed a complete loss of VP determination. More modest effects were observed in the other lobes, including decreased number of ductal buds in the dorsal and lateral prostates of newborn Noggin-/- males. BMP4 and BMP7 have been shown to inhibit ductal budding and outgrowth by negatively regulating epithelial cell proliferation. We show here that NOGGIN can neutralize budding inhibition by BMP4 and rescues branching morphogenesis of BMP4-exposed UGS in organ culture and show that the effects of BMP4 and NOGGIN activities converge on P63+ epithelial cells located at nascent duct tips. Together, these studies show that the BMP-NOGGIN axis regulates patterning of the ventral prostate, regulates ductal budding, and controls proliferation of P63+ epithelial cells in the nascent ducts of developing mouse prostate. PMID:18028901

Ductal recanalization and stenting for late presenters with TGA intact ventricular septum

PubMed Central

Kothari, Shyam S; Ramakrishnan, Sivasubramanian; Senguttuvan, Nagendra Boopathy; Gupta, Saurabh Kumar; Bisoi, Akshay K

2011-01-01

Introduction: The ideal management strategy for patients presenting late with transposition of great arteries (TGA), intact ventricular septum (IVS), and regressed left ventricle (LV) is not clear. Primary switch, two-stage switch, and Senning operation are the options. Left ventricular retraining prior to arterial switch by ductal stenting may be effective, but the experience is very limited. Methods: Five of six children aged 3–6 months with TGA-IVS and regressed LV underwent recanalization and transcatheter stenting of ductus arteriosus. The ductal stent was removed during arterial switch surgery. Results: The procedure was successful in 5/6 patients. All the patients had totally occluded ductus and needed recanalization with coronary total occlusion hardware. The ductus was dilated and stented with coronary stents. In all the patients, there was significant luminal narrowing despite adequate stent placement and deployment. Two patients needed reintervention for abrupt closure of the stent. Ductal stenting resulted in left ventricular preparedness within 7–14 days. One patient died of progressive sepsis after 14 days of stenting, even though the LV was prepared. Four patients underwent successful uneventful arterial switch surgery. During surgery, it was observed that the mucosal folds of duct were protruding through the struts of the stent in one patient. Conclusions: Ductal stenting is a good alternative strategy for left ventricular retraining in TGA with regressed LV even in patients with occluded ducts. PMID:21976872

Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes

PubMed Central

Zhang, Mingfeng; Lin, Qing; Qi, Tong; Wang, Tiankun; Chen, Ching-Cheng; Riggs, Arthur D.; Zeng, Defu

2016-01-01

We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9+ (Sox9+) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9+ ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9+ ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300–450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9+ ductal cell differentiation into β cells in adult mice. PMID:26733677

Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell lymphoma and reactive lymphoid hyperplasia

PubMed Central

Grier, David D; Al-Quran, Samer Z; Cardona, Diana M; Li, Ying; Braylan, Raul C

2012-01-01

The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes. PMID:22400070

Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma

DOE PAGES

Connor, Ashton A.; Denroche, Robert E.; Jang, Gun Ho; ...

2016-10-20

Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. In addition, advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease.

Diet-induced inflammation and mammary ductal development: Alternative activation of estrogen-dependent stromal-epithelial signaling

USDA-ARS?s Scientific Manuscript database

The mechanisms controlling allometric development of the mammary ductal tree have largely been defined through key studies in rodent model systems. The development of this system is known to depend on the integrated actions of pituitary and ovarian hormones, locally produced growth factors, extracel...

Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.

PubMed

Dunphy, Cherie H; Galambos, Csaba; Polski, Jacek M; Evans, H Lance; Gardner, Laura J; Grosso, Leonard E; Montone, Kathleen T

2002-03-01

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?

PubMed

Gilissen, L P L; Derijks, L J J; Driessen, A; Bos, L P; Hooymans, P M; Stockbrügger, R W; Engels, L G J B

2007-02-01

6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging. Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine. 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity.

Clinical associations of hepatic stellate cell (HSC) hyperplasia.

PubMed

Mounajjed, Taofic; Graham, Rondell P; Sanderson, Schuyler O; Smyrk, Thomas C

2014-07-01

Hepatic stellate cell (HSC) hyperplasia has been principally attributed to hypervitaminosis A. There are sporadic reports of HSC hyperplasia in other conditions such as chronic biliary disease and hepatitis C, but clinical associations of this entity have not been studied in detail. We aimed to investigate the clinical associations of HSC hyperplasia aside from hypervitaminosis A. We identified 34 patients whose liver histology showed HSC hyperplasia. We reviewed the liver samples; additional histologic findings in addition to HSC hyperplasia were consolidated into a histologic diagnosis. We collected clinical, laboratory, and radiologic data; the histologic diagnosis was combined with this data to reach an "overall diagnosis." Four patients had hypervitaminosis A (all native livers). In native livers (n = 24), HSC hyperplasia also occurred in association with drug-induced hepatitis [n = 6, niacin was the most common inducing agent (n = 3)], reactive hepatitis (n = 4), chronic hepatitis C (n = 4), autoimmune hepatitis (n = 3), steatohepatitis (n = 1), chronic biliary disease (n = 1), and portal venopathy (n = 1). In liver allografts (n = 10), HSC hyperplasia was seen in protocol biopsies without other significant abnormalities (n = 5), chronic biliary disease (n = 4), and acute cellular rejection (n = 1). All patients used medications (total of 99) and 82 % were on multiple medications. HSC hyperplasia is an uncommon and relatively nonspecific finding that most commonly occurs in multimedicated patients, often in the absence of hypervitaminosis A. Associated conditions include drug toxicity (such as niacin), post-liver transplant setting, reactive hepatitis (due to systemic illness or inflammatory disorders of the gastrointestinal tract), and chronic liver disease.

Lack of Effect of 94 GHz Radio Frequency Radiation Exposure in an Animal Model of Skin Carcinogenesis

DTIC Science & Technology

2001-10-01

villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells; although benign, papillomas are premalignant lesions that will...thin stratum corneum; 1, minimal hyperplasia , epithelium ~4–6 cell layers thick; 2, minimal to mild hyperplasia , variable amounts of hyperplasia ...across the specimen, areas fitting each description present; 3, mild hyperplasia , epithelium ~7–9 cell layers thick or epithelial layer composed of ~4–6

[Nesidioblastosis in the adult: a case report].

PubMed

Ramírez-González, Luis Ricardo; Sotelo-Álvarez, Jorge Arturo; Rojas-Rubio, Priscila; Macías-Amezcua, Michel Dassaejv; Orozco-Rubio, Rafael; Fuentes-Orozco, Clotilde

2015-01-01

Nesidioblastosis is a rare cause of endocrine disease which represents between 0.5% - 5% of cases. This has been associated with other conditions, such as in patients previously treated with insulin or sulfonylurea, in anti-tumour activity in pancreatic tissue of patients with insulinoma, and in patients with other tumours of the Langerhans islet cells. In adults it is presented as a diffuse dysfunction of β cells of unknown cause. The case concerns 46 year-old female, with a history of Sheehan syndrome of fifteen years of onset, and with repeated events characterized with hypoglycaemia in the last three years. Body scan was performed with octreotide, revealing an insulinoma in the pancreatic region. A distal pancreatectomy was performed on the patient. The study reported a pancreatic fragment 8.5 × 3 × 1.5 cm with abnormal proliferation of pancreatic islets in groups of varying size, some of them in relation to the ductal epithelium. Histopathology study was showed positive for chromogranin, confirmed by positive synaptophysin, insulin and glucagon, revealing islet hyperplasia with diffuse nesidioblastosis with negative malignancy. The patient is currently under metabolic control and with no remission of hypoglycaemic events. Nesidioblastosis is a disease of difficult diagnosis should be considered in all cases of failure to locate an insulinoma, as this may be presented in up to 4% of persistent hyperinsulinaemic hypoglycaemia. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Recent advances in prostate development and links to prostatic diseases

PubMed Central

Powers, Ginny L.

2013-01-01

The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signalling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression (SAGE), expression profiling microarrays, and other large scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multi-lab projects including the Genitourinary Developmental Molecular Atlas Project (GUDMAP) has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases. PMID:23335485

Nuclear morphometry in histological specimens of canine prostate cancer: Correlation with histological subtypes, Gleason score, methods of collection and survival time.

PubMed

Di Donato, Guido; Laufer-Amorim, Renée; Palmieri, Chiara

2017-10-01

Ten normal prostates, 22 benign prostatic hyperplasia (BPH) and 29 prostate cancer (PC) were morphometrically analyzed with regard to mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND), coefficient of variation of the nuclear area (NACV), mean nuclear diameter maximum (MDx), mean nuclear diameter minimum (MDm), mean nuclear form ellipse (MNFe) and form factor (FF). The relationship between nuclear morphometric parameters and histological type, Gleason score, methods of sample collection, presence of metastases and survival time of canine PC were also investigated. Overall, nuclei from neoplastic cells were larger, with greater variation in nuclear size and shape compared to normal and hyperplastic cells. Significant differences were found between more (small acinar/ductal) and less (cribriform, solid) differentiated PCs with regard to FF (p<0.05). MNA, MNP, MND, MDx, and MDm were significantly correlated with the Gleason score of PC (p<0.05). MNA, MNP, MDx and MNFe may also have important prognostic implications in canine prostatic cancer since negatively correlated with the survival time. Biopsy specimens contained nuclei that were smaller and more irregular in comparison to those in prostatectomy and necropsy specimens and therefore factors associated with tissue sampling and processing may influence the overall morphometric evaluation. The results indicate that nuclear morphometric analysis in combination with Gleason score can help in canine prostate cancer grading, thus contributing to the establishment of a more precise prognosis and patient's management. Copyright © 2017 Elsevier Ltd. All rights reserved.

“Stealth dissemination” of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma

USDA-ARS?s Scientific Manuscript database

Circulating tumor cells (CTCs) appear to be involved in early dissemination of many cancers, although which characteristics are important in metastatic spread are not clear. Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal a...

Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?

PubMed

Limaiem, F; Khadhar, A; Hassan, F; Bouraoui, S; Lahmar, A; Mzabi, S

2013-12-01

A 77-year-old female patient with a medical history significant for hypertension and epilepsy presented with right breast pain of 6-months duration. Examination revealed a hard sub-areola tender mass with irregular borders associated with mild right nipple retraction. Mammography showed a 2.2 x 2.4 cm stellate mass of the right breast. Ultrasound-guided core biopsies of the tumour were performed. Pathological examination revealed a grade II infiltrating ductal carcinoma. The patient underwent right radical mastectomy with homolateral axillary lymphadenectomy. Histological examination of the surgical specimen revealed grade II infiltrating ductal carcinoma concomitant with granulomatous lobular mastitis. To the best of our knowledge, the coexistence of granulomatous lobular mastitis and ductal carcinoma has been described only twice in the English language literature. The theory that chronic inflammation leads to cancer is well documented. Whether our patient had developed cancer from granulomatous lobular mastitis or otherwise is a matter of debate until more cases are encountered and more research is done in the area of breast cancer pathogenesis with regards to it arising from granulomatous lobular mastitis.

Mammographic breast density and risk of breast cancer in women with atypical hyperplasia: an observational cohort study from the Mayo Clinic Benign Breast Disease (BBD) cohort.

PubMed

Vierkant, Robert A; Degnim, Amy C; Radisky, Derek C; Visscher, Daniel W; Heinzen, Ethan P; Frank, Ryan D; Winham, Stacey J; Frost, Marlene H; Scott, Christopher G; Jensen, Matthew R; Ghosh, Karthik; Manduca, Armando; Brandt, Kathleen R; Whaley, Dana H; Hartmann, Lynn C; Vachon, Celine M

2017-01-31

Atypical hyperplasia (AH) and mammographic breast density (MBD) are established risk factors for breast cancer (BC), but their joint contributions are not well understood. We examine associations of MBD and BC by histologic impression, including AH, in a subcohort of women from the Mayo Clinic Benign Breast Disease Cohort. Women with a diagnosis of BBD and mammogram between 1985 and 2001 were eligible. Histologic impression was assessed via pathology review and coded as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and AH. MBD was assessed clinically using parenchymal pattern (PP) or BI-RADS criteria and categorized as low, moderate or high. Percent density (PD) was also available for a subset of women. BC and clinical information were obtained by questionnaires, medical records and the Mayo Clinic Tumor Registry. Women were followed from date of benign biopsy to BC, death or last contact. Standardized incidence ratios (SIRs) compared the observed number of BCs to expected counts. Cox regression estimated multivariate-adjusted MBD hazard ratios. Of the 6271 women included in the study, 1132 (18.0%) had low MBD, 2921 (46.6%) had moderate MBD, and 2218 (35.4%) had high MBD. A total of 3532 women (56.3%) had NP, 2269 (36.2%) had PDWA and 470 (7.5%) had AH. Over a median follow-up of 14.3 years, 528 BCs were observed. The association of MBD and BC risk differed by histologic impression (p-interaction = 0.03), such that there was a strong MBD and BC association among NP (p < 0.001) but non-significant associations for PDWA (p = 0.27) and AH (p = 0.96). MBD and BC associations for AH women were not significant within subsets defined by type of MBD measure (PP vs. BI-RADS), age at biopsy, number of foci of AH, type of AH (lobular vs. ductal) and body mass index, and after adjustment for potential confounding variables. Women with atypia who also had high PD (>50%) demonstrated marginal evidence of increased BC risk (SIR 4.98), but results were not statistically significant. We found no evidence of an association between MBD and subsequent BC risk in women with AH.

Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17 beta or diethylstilbestrol.

PubMed

Bosland, M C; Ford, H; Horton, L

1995-06-01

This study determined the incidence of prostate adenocarcinoma following long-term treatment of NBL and Sprague-Dawley rats with estradiol-17 beta or diethylstilbestrol (DES) plus testosterone and it defined the origin of these tumors. NBL and Sprague-Dawley rats were treated with two Silastic tubing implants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long filling of testosterone and one implant containing a 1 cm long filling of estradiol-17 beta or DES. Control animals received empty implants. Treated animals were killed when moribund and controls were killed at 91 (NBL) or 75 (Sprague-Dawley) weeks after initiation of treatment and accessory sex glands were sampled for histopathological examination of multiple step sections. Prostatic adenocarcinoma occurred in 100% of NBL rats after treatment with estradiol-17 beta or DES plus testosterone for 44 and 59 weeks (group means) respectively. Adenocarcinoma incidences were lower in Sprague-Dawley rats. The adenocarcinomas were small, microscopic, invasive tumors and they were spatially closely associated with the periurethral ducts of the dorsal, lateral and/or anterior (= coagulating gland) prostate, but never with the ducts of the ventral lobe and seminal vesicles. One adenocarcinoma was of uncertain origin. Duct-acinar dysplastic lesions occurred in the periphery of the dorsal and lateral prostate of all hormone-treated NBL and many Sprague-Dawley rats, but did not appear to give rise to carcinoma. Although some adenocarcinomas were contiguous with dysplastic ducts of the peripheral dorsolateral prostate, the main mass of these neoplasms was located in the periurethral area. Also, most adenocarcinomas were only connected with the periurethral ducts, in which atypical hyperplasia occurred following hormone treatment for 36 weeks or longer. Thus atypical hyperplasia of the periurethral prostate ducts, but not peripheral duct-acinar dysplasia, appeared to be the likely precursor of the induced carcinomas. Testosterone plus DES, but not estradiol-17 beta, induced marked dysplasia-like lesions in the acini of the ventral prostate of all NBL and many Sprague-Dawley rats. These lesions had progressed to carcinoma in situ (or adenoma) in 46% of NBL rats.

Management of adolescents with congenital adrenal hyperplasia

PubMed Central

Merke, Deborah P; Poppas, Dix P

2014-01-01

The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

Reversion of gingival hyperplasia in a heart transplant patient upon interruption of cyclosporine therapy.

PubMed

Somacarrera, M L; Lucas, M; Acero, J

1996-01-01

A heart transplant patient undergoing a combined cyclosporine and prednisone treatment was monitored during the 18 months following transplantation. A complete oral and dental examination was performed in each of the first six months after transplantation, and then in the 9th, 12th, 15th, and 18th months. The data collected included gingival hyperplasia secondary to cyclosporine use, and clinical and periodontal variables. Histological studies were also conducted on gingival tissue samples in months 1, 3, 9, 15, and 18. Cyclosporine treatment was replaced by azathioprine treatment in month 10 because the patient was experiencing nephrotoxicity. Between months 9 and 18, gingival hyperplasia regressed by 26.5% due to a reduction in the fibrous connective tissue mass, fibroblasts, and inflammatory infiltration. The control group included 13 heart transplant patients subject to equivalent conditions except discontinuance of cyclosporine treatment; seven of the patients had developed hyperplasia by month 9. Average hyperplasia in the control group increased by 2% between months 9 and 18; only one patient showed a 6.2% decrease in hyperplasia. This provides further evidence for the causal relationship between cyclosporine therapy and gingival hyperplasia, and suggests that this side-effect is reversible.

Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.

PubMed

Sugiyama, Michiko; Hasebe, Takahiro; Shimada, Hiroko; Takeuchi, Hideki; Shimizu, Kyoko; Shimizu, Michio; Yasuda, Masanori; Ueda, Shigeto; Shigekawa, Takashi; Osaki, Akihiko; Saeki, Toshiaki

2015-06-01

We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. Copyright © 2015 Elsevier Inc. All rights reserved.

Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study.

PubMed

Williams, Lindsay A; Nichols, Hazel B; Hoadley, Katherine A; Tse, Chiu Kit; Geradts, Joseph; Bell, Mary Elizabeth; Perou, Charles M; Love, Michael I; Olshan, Andrew F; Troester, Melissa A

2018-01-01

Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+). In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype. Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.

Early signs that predict later haemodynamically significant patent ductus arteriosus.

PubMed

Engür, Defne; Deveci, Murat; Türkmen, Münevver K

2016-03-01

Our aim was to determine the optimal cut-off values, sensitivity, specificity, and diagnostic power of 12 echocardiographic parameters on the second day of life to predict subsequent ductal patency. We evaluated preterm infants, born at ⩽32 weeks of gestation, starting on their second day of life, and they were evaluated every other day until ductal closure or until there were clinical signs of re-opening. We measured transductal diameter; pulmonary arterial diastolic flow; retrograde aortic diastolic flow; pulsatility index of the left pulmonary artery and descending aorta; left atrium and ventricle/aortic root ratio; left ventricular output; left ventricular flow velocity time integral; mitral early/late diastolic flow; and superior caval vein diameter and flow as well as performed receiver operating curve analysis. Transductal diameter (>1.5 mm); pulmonary arterial diastolic flow (>25.6 cm/second); presence of retrograde aortic diastolic flow; ductal diameter by body weight (>1.07 mm/kg); left pulmonary arterial pulsatility index (⩽0.71); and left ventricle to aortic root ratio (>2.2) displayed high sensitivity and specificity (p0.9). Parameters with moderate sensitivity and specificity were as follows: left atrial to aortic root ratio; left ventricular output; left ventricular flow velocity time integral; and mitral early/late diastolic flow ratio (p0.05) had low diagnostic value. Left pulmonary arterial pulsatility index, left ventricle/aortic root ratio, and ductal diameter by body weight are useful adjuncts offering a broader outlook for predicting ductal patency.

Immunohistochemical localization of cannabinoid receptor 1 (CB1) in the submandibular gland of mice under normal conditions and when stimulated by isoproterenol or carbachol.

PubMed

Thoungseabyoun, Wipawee; Tachow, Apussara; Pakkarato, Sawetree; Rawangwong, Atsara; Krongyut, Suthankamon; Sakaew, Waraporn; Kondo, Hisatake; Hipkaeo, Wiphawi

2017-09-01

We wished to investigate the subcellular localization of CB1, a receptor for the endocannabinoids in mouse submandibular glands (SMGs) under normal conditions and when stimulated by adrenergic or cholinergic agonists. SMGs of both male and female adult mice were utilized for immunoblotting and immuno-light and -electron microscopic analyses. Isoproterenol and carbachol were used as adrenergic and cholinergic stimulants, respectively. SMGs were examined at 15, 30, 60 and 120min after intraperitoneal injection of these agents. Selective localization of intense immunoreactivity for CB1 in the granular convoluted ductal cells was confirmed by immunoblotting and the antigen absorption test. In SMGs of control male mice, CB1-immunoreactivity was evident on the basolateral plasma membranes, including the basal infoldings, but was absent on the apical membranes in the ductal cells. Localization and intensity of CB1-immunoreactivity were essentially the same in SMGs of female mice. The immunoreactivity was transiently localized in the apical plasmalemma of some acinar and granular ductal cells of male SMGs shortly after stimulation by isoproterenol, but not by carbachol. The present finding suggests that CB1 functions primarily in the basolateral membranes of the granular convoluted ductal cells of SMGs under normal conditions, and that the CB1 can function additionally in the apical membrane of acinar and granular ductal cells for modulation of the saliva secretory condition via adrenoceptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media

PubMed Central

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B.; Jansen, Sanaz A.; Macleod, Kay; Conzen, Suzanne D.; Karczmar, Gregory S.

2014-01-01

The purpose of this study was to use high resolution 3D MRI to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12–20 weeks (n = 12), were used in this study. A 34G, 45° tip Hamilton needle with a 25uL Hamilton syringe was inserted into the tip of the nipple. Approximately 20–25uL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p < 0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p < 0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. PMID:25179139

Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

PubMed Central

Hsu, Jong-Hau; Oishi, Peter; Wiseman, Dean A.; Hou, Yali; Chikovani, Omar; Datar, Sanjeev; Sajti, Eniko; Johengen, Michael J.; Harmon, Cynthia; Black, Stephen M.

2010-01-01

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2–4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000–1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction. PMID:20363848

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

PubMed

Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2012-03-10

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

PubMed

Liao, Dezhong Joshua; Wang, Yong; Wu, Jiusheng; Adsay, Nazmi Volkan; Grignon, David; Khanani, Fayyaz; Sarkar, Fazlul H

2006-07-05

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgf alpha-ES lines, TGF alpha transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2-7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al 1. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgf alpha-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgf alpha/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

PubMed

Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

2015-11-01

Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevention of Bronchial Hyperplasia by EGFR Pathway Inhibitors in an Organotypic Culture Model

PubMed Central

Lee, Jangsoon; Ryu, Seung-Hee; Kang, Shin Myung; Chung, Wen-Cheng; Gold, Kathryn Ann; Kim, Edward S.; Hittelman, Walter N.; Hong, Waun Ki; Koo, Ja Seok

2011-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor. The current study was designed to determine the molecular mechanisms that control bronchial epithelium hyperplasia. Using primary normal human tracheobronchial epithelial (NHTBE) cells cultured using the 3-dimensional organotypic method, we found that the epidermal growth factor receptor (EGFR) ligands EGF, transforming growth factor-alpha, and amphiregulin induced hyperplasia, as determined by cell proliferation and multilayered epithelium formation. We also found that EGF induced increased cyclin D1 expression, which plays a critical role in bronchial hyperplasia; this overexpression was mediated by activating the mitogen-activated protein kinase pathway but not the phosphoinositide 3-kinase/Akt signaling pathway. Erlotinib, an EGFR tyrosine kinase inhibitor, and U0126, a MEK inhibitor, completely inhibited EGF-induced hyperplasia. Furthermore, a promoter analysis revealed that the activator protein-1 transcription factor regulates EGF-induced cyclin D1 overexpression. Activator protein-1 depletion using siRNA targeting its c-Jun component completely abrogated EGF-induced cyclin D1 expression. In conclusion, we demonstrated that bronchial hyperplasia can be modeled in vitro using primary NHTBE cells maintained in a 3-dimensional (3-D) organotypic culture. EGFR and MEK inhibitors completely blocked EGF-induced bronchial hyperplasia, suggesting that they have a chemopreventive role. PMID:21505178

Prognostic significance of atypical papillary urothelial hyperplasia.

PubMed

Swierczynski, Sharon L; Epstein, Jonathan I

2002-05-01

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms. Copyright 2002, Elsevier Science (USA). All rights reserved.

Guinea pig ductus arteriosus. II - Irreversible closure after birth.

NASA Technical Reports Server (NTRS)

Fay, F. S.; Cooke, P. H.

1972-01-01

To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2011-10-01

fibroblast   growth   factor   receptors  and  their  prognostic...AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2008 – 14 September 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth

Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient.

PubMed

Ricciuti, Biagio; Leonardi, Giulia Costanza; Ravaioli, Noemi; De Giglio, Andrea; Brambilla, Marta; Prosperi, Enrico; Ribacchi, Franca; Meacci, Marialuisa; Crinò, Lucio; Maiettini, Daniele; Chiari, Rita; Metro, Giulio

2016-09-01

Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis.

The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance

PubMed Central

Schnitt, Stuart J

2003-01-01

Flat epithelial atypia is a descriptive term that encompasses lesions of the breast terminal duct lobular units in which variably dilated acini are lined by one to several layers of epithelial cells, which are usually columnar in shape and which display low-grade cytologic atypia. Observational studies have suggested that at least some of these lesions may represent either a precursor of ductal carcinoma in situ (DCIS) or the earliest morphological manifestation of DCIS. In contrast, the limited available clinical follow-up data suggest that the risk of both local recurrence and progression of these lesions to invasive cancer is extremely low, supporting the notion that categorizing such lesions as 'clinging carcinoma' and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions. PMID:12927037

[Quantitative characterization of nuclear polymorphism of the epithelial cells in fibroadenomatosis and cancer of the breast].

PubMed

Ganina, K P; Petunin, Iu I; Timoshenko, Ia G

1989-01-01

A method for quantitative analysis of epithelial cell nuclear polymorphism was suggested, viz. identification of general statistical population using Petunin's criterion. This criterion was employed to assess heterogeneity of visible surface of interphase epithelial cell nuclei and to assay nuclear DNA level in fibroadenomatous hyperplasia and cancer of the breast. Heterogeneity index (h), alongside with other parameters, appeared useful for quantitative assessment of the disease: heterogeneity index values ranging 0.1-0.4 point to pronounced heterogeneity of epithelial cell nucleus surface and DNA level, and are suggestive of malignant transformation of tissue, whereas benign proliferation of the epithelium is usually characterized by 0.4 less than h less than or equal to 0.9.

Antenatal Bartter Syndrome: A Review

PubMed Central

Bhat, Y. Ramesh; Vinayaka, G.; Sreelakshmi, K.

2012-01-01

Antenatal Bartter syndrome (ABS) is a rare autosomal recessive renal tubular disorder. The defective chloride transport in the loop of Henle leads to fetal polyuria resulting in severe hydramnios and premature delivery. Early onset, unexplained maternal polyhydramnios often challenges the treating obstetrician. Increasing polyhydramnios without apparent fetal or placental abnormalities should lead to the suspicion of this entity. Biochemical analysis of amniotic fluid is suggested as elevated chloride level is usually diagnostic. Awareness, early recognition, maternal treatment with indomethacin, and amniocentesis allow the pregnancy to continue. Affected neonates are usually born premature, have postnatal polyuria, vomiting, failure to thrive, hypercalciuria, and subsequently nephrocalcinosis. Hypokalemia, metabolic alkalosis, secondary hyperaldosteronism and hyperreninaemia are other characteristic features. Volume depletion due to excessive salt and water loss on long term stimulates renin-angiotensin-aldosterone system resulting in juxtaglomerular hyperplasia. Clinical features and electrolyte abnormalities may also depend on the subtype of the syndrome. Prenatal diagnosis and timely indomethacin administration prevent electrolyte imbalance, restitute normal growth, and improve activity. In this paper, authors present classification, pathophysiology, clinical manifestations, laboratory findings, complications, and prognosis of ABS. PMID:22518185

Proteus syndrome: association with gingival hyperplasia.

PubMed

Arendorf, T M; Hanslo, B

1995-09-01

A 9-year old Black boy with gigantism of the hands and feet, and recurrent gingival hyperplasia, diagnosed as Proteus syndrome is presented. The oral manifestations of this syndrome are described. To the best of our knowledge, this is the first reported case of gingival hyperplasia associated with Proteus syndrome.

Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.

PubMed

Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Julião, M; Gouveia, H; Sofia, C

2012-06-01

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).

Ovarian hilus-cell hyperplasia and high serum testosterone in a patient with postmenopausal virilization.

PubMed

Delibasi, Tuncay; Erdogan, Murat F; Serinsöz, Ebru; Kaygusuz, Gulsah; Erdogan, Gurbuz; Sertçelik, Ayse

2007-09-01

To describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia. We present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature. A 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient's plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum. In the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered.

[Differential diagnosis of papillary carcinomas of the thyroid, using image analysis and three dimensional reconstruction from serial sections].

PubMed

Holschbach, A; Kriete, A; Schäffer, R

1990-01-01

Papillae with fibrovascular cores are characteristic of papillary carcinoma of the thyroid. Papillae may be found in diffuse hyperplasia, nodular hyperplasia, Hashimoto's disease and follicular adenoma. Tissues from ten benign hyperplasias and ten papillary carcinomas were reconstructed from serial sections with three dimensional reconstruction programs. Significant qualitative and quantitative differences were found between the hyperplasia and the carcinoma. The principal differences between papillae of papillary carcinoma and hyperplasia were more clearly seen in the three dimensional reconstruction, than by means of morphometric methods. Certain criteria, e.g. the volume of papillae, were useful only with regard to the third dimension. Nevertheless, three dimensional reconstruction of biological tissue is a time consuming procedure which is not yet suitable for routine examination.

Acute Toxoplasma gondii infection in children with reactive hyperplasia of the cervical lymph nodes.

PubMed

Bilal, Jalal A; Alsammani, Mohamed A; Ahmed, Mohamed I

2014-07-01

To determine the seroprevalence of Toxoplasma gondii (T. gondii) in children with reactive hyperplasia of the cervical lymph nodes. This cross-sectional prospective study was conducted in Khartoum Children Emergency Hospital, Khartoum, Sudan between January 2010 and April 2011. Eighty children with cervical lymphadenopathy were selected using random sampling. Their lymph nodes were aspirated for cytology, and a blood sample was collected from all patients for routine laboratory analysis and T. gondii IgG and IgM antibodies. Among 80 children with cervical lymphadenopathy, 60 (75%) had non-specific reactive hyperplasia. The seroprevalence of T. gondii among children with cervical lymphadenopathy was 27.5% (n=22), and the seropositivity of acute T. gondii among those with reactive hyperplasia was 36.7% (n=22/60). Lymph nodes in the T. gondii positive group were mobile and warm (p<0.05). The clinical features and laboratory tests were insignificant predictors of acute T. gondii infection with reactive hyperplasia of the cervical lymph nodes. The prevalence of acute T. gondii infection is high among children with non-specific reactive hyperplasia of the cervical lymph nodes. Routine laboratory studies are not helpful in the diagnosis of T. gondii infection with reactive hyperplasia of the lymph nodes however, serological studies may be requested prior to invasive procedures.

Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography-tandem mass spectrometry.

PubMed

Janzen, Nils; Sander, Stefanie; Terhardt, Michael; Steuerwald, Ulrike; Peter, Michael; Das, Anibh M; Sander, Johannes

2011-12-11

Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression >0.992. Absolute recovery was >64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was <3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program. Copyright © 2011 Elsevier Inc. All rights reserved.

Different cytokeratin and neuronal cell adhesion molecule staining patterns in focal nodular hyperplasia and hepatic adenoma and their significance

PubMed Central

Iyer, Anita; Robert, Marie E.; Bifulco, Carlo B.; Salem, Ronald R.; Jain, Dhanpat

2013-01-01

Summary Differentiating focal nodular hyperplasia from hepatic adenoma can be challenging. Cytokeratin 7, neuronal cell adhesion molecule, and cytokeratin 19 are differentially expressed in hepatocytes, biliary epithelium, and possibly hepatic progenitor/stem cells. CD34 is known to have altered expression patterns in the hepatic endothelium in conditions associated with abnormal perfusion and in hepatocellular carcinoma. The purpose of this study was to examine the expression pattern of these markers in focal nodular hyperplasia and hepatic adenoma and assess their diagnostic use. Ten resection specimens each of hepatic adenoma and focal nodular hyperplasia (including a case of telangiectatic focal nodular hyperplasia) were selected for the study. Immunohistochemical analysis was performed using antibodies against cytokeratin 7, cytokeratin 19, neuronal cell adhesion molecule, and CD34 on formalin-fixed, paraffin-embedded sections from each case. The staining patterns and intensity for each marker were analyzed. In hepatic adenoma, the cytokeratin 7 stain revealed strong positivity in hepatocytes in patches, with a gradual decrease in the staining intensity as the cells differentiated towards mature hepatocytes. Although bile ducts were typically absent in hepatic adenoma, occasional ductules could be identified with cytokeratin 7 stain. In focal nodular hyperplasia, cytokeratin 7 showed strong staining of the biliary epithelium within the fibrous septa and staining of the peripheral hepatocytes of most lobules that was focal and weaker than hepatic adenoma. Cytokeratin 19 and neuronal cell adhesion molecule showed patchy and moderate staining in the biliary epithelium of the ductules in focal nodular hyperplasia. While in the hepatic adenoma, cytokeratin 19 showed only rare positivity in occasional cells within ductules, and neuronal cell adhesion molecule marked occasional isolated cells in the lesion. CD34 showed staining of sinusoids in the inflow areas (periportal areas) in both focal nodular hyperplasia and hepatic adenoma. One case of telangiectatic focal nodular hyperplasia revealed both hepatic adenoma–like and focal nodular hyperplasia–like staining patterns. Distinct cytokeratin 7, cytokeratin 19, and neuronal cell adhesion molecule staining patterns are seen in hepatic adenoma and focal nodular hyperplasia possibly suggest activation of different subsets of hepatic progenitor/stem cell and can be diagnostically useful. PMID:18602664

Ductal stenting retrains the left ventricle in transposition of great arteries with intact ventricular septum.

PubMed

Sivakumar, Kothandam; Francis, Edwin; Krishnan, Prasad; Shahani, Jagdish

2006-11-01

In late presenters with transposition of the great arteries, intact ventricular septum, and regressing left ventricle, left ventricular retraining by pulmonary artery banding and aortopulmonary shunt is characterized by a stormy postoperative course and high costs. Ductal stenting in the cardiac catheterization laboratory is conceptualized to retrain the left ventricle with less morbidity. Recanalization and transcatheter stenting of patent ductus arteriosus was performed in patients with transposition to induce pressure and volume overload to the regressing left ventricle. Serial echocardiographic monitoring of left ventricular shape, mass, free wall thickness, and volumes was done, and once the left ventricle was adequately prepared, an arterial switch was performed. The ductal stent was removed and the remaining surgical steps were similar to a 1-stage arterial switch operation. Postoperative course, need for inotropic agents, and left ventricular function were monitored. Ductal stenting in 2 patients aged 3 months resulted in improvement of indexed left ventricular mass from 18.9 to 108.5 g/m2, left ventricular free wall thickness from 2.5 to 4.8 mm, and indexed left ventricular volumes from 7.6 to 29.5 mL/m2 within 3 weeks. Both patients underwent arterial switch (bypass times 125 and 158 minutes) uneventfully, needed inotropic agents and ventilatory support for 3 days, and were discharged in 8 and 10 days. Ductal stenting is a less morbid method of left ventricular retraining in transposition of the great arteries with regressed left ventricle. Its major advantages lie in avoiding pulmonary artery distortion and neoaortic valve regurgitation resulting from banding and also in avoiding thoracotomy.

Pig Pancreas Anatomy: Implications for Pancreas Procurement, Preservation, and Islet Isolation

PubMed Central

Ferrer, Joana; Scott, William E; Weegman, Bradley P; Suszynski, Thomas M; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

2009-01-01

Background Islet transplantation is emerging as a treatment option for selected patients with type 1 diabetes. The limited human islet supply from cadavers and poor islet yield and quality remain substantial impediments to progress in the field. Use of porcine islets holds great promise for large-scale application of islet transplantation. Consistent isolation of porcine islets is dependent on advances in pancreas procurement and preservation, and islet isolation requiring detailed knowledge of the porcine pancreatic anatomy. The primary aim of this study was to describe the vascular and ductal anatomy of the porcine pancreas in order to guide and improve organ preservation and enzyme perfusion. Methods Pancreata were removed by en bloc viscerectomy from 65 female Landrace pigs. Results 15% of organs exhibited inconsistent vascular branching from the celiac trunk. All organs had uniform patterns of branching at the superior mesenteric artery. The superior and inferior mesenteric veins (IMV) merged to become the portal vein in all but one case in which the IMV drained into the splenic vein. 97% of pancreata had three lobes: duodenal (DL), connecting (CL), and splenic (SL); 39% demonstrated ductal communication between the CL and the other two lobes; 50% had ductal communication only between the CL and DL; and 11% presented other types of ductal delineation. Conclusions Accounting for the variations in vascular and ductal anatomy, as detailed in this study, will facilitate development of protocols for preservation, optimal enzyme administration, and pancreas distention and digestion, and ultimately lead to substantial improvements in isolation outcomes. PMID:19077881

The anti-tumor effect of HDAC inhibition in a human pancreas cancer model is significantly improved by the simultaneous inhibition of cyclooxygenase 2.

PubMed

Peulen, Olivier; Gonzalez, Arnaud; Peixoto, Paul; Turtoi, Andrei; Mottet, Denis; Delvenne, Philippe; Castronovo, Vincent

2013-01-01

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death worldwide, with no satisfactory treatment to date. In this study, we tested whether the combined inhibition of cyclooxygenase-2 (COX-2) and class I histone deacetylase (HDAC) may results in a better control of pancreatic ductal adenocarcinoma. The impact of the concomitant HDAC and COX-2 inhibition on cell growth, apoptosis and cell cycle was assessed first in vitro on human pancreas BxPC-3, PANC-1 or CFPAC-1 cells treated with chemical inhibitors (SAHA, MS-275 and celecoxib) or HDAC1/2/3/7 siRNA. To test the potential antitumoral activity of this combination in vivo, we have developed and characterized, a refined chick chorioallantoic membrane tumor model that histologically and proteomically mimics human pancreatic ductal adenocarcinoma. The combination of HDAC1/3 and COX-2 inhibition significantly impaired proliferation of BxPC-3 cells in vitro and stalled entirely the BxPC-3 cells tumor growth onto the chorioallantoic membrane in vivo. The combination was more effective than either drug used alone. Consistently, we showed that both HDAC1 and HDAC3 inhibition induced the expression of COX-2 via the NF-kB pathway. Our data demonstrate, for the first time in a Pancreatic Ductal Adenocarcinoma (PDAC) model, a significant action of HDAC and COX-2 inhibitors on cancer cell growth, which sets the basis for the development of potentially effective new combinatory therapies for pancreatic ductal adenocarcinoma patients.

Initial experience of automated breast volume scanning (ABVS) and ultrasound elastography in predicting breast cancer subtypes and staging.

PubMed

Wang, Xiao-Lei; Tao, Lin; Zhou, Xian-Li; Wei, Hong; Sun, Jia-Wei

2016-12-01

Breast cancer is a heterogeneous disease consisting of distinct histopathological subtypes with different clinical outcomes. In this article, we identified the automated breast volume scanning (ABVS) and shear wave velocity (SWV) characteristics of different pathological types of breast carcinoma. A retrospective review of both ABVS and SWV imaging of 118 consecutive breast masses was performed. The imaging features of both techniques were assessed with reference to histopathological results. Echo heterogeneity with a smooth and lobulated margin was a significant feature more frequently found in mucinous carcinoma groups (100%, P < 0.05). Between different stages of ductal carcinoma, echo homogeneity was more likely in high-grade ductal carcinomas (P < 0.05). SWV differences existed between inside tumor areas and either tumor boundary or tissues outside the tumors (P < 0.05), and values differed between different breast carcinoma stages. The central and tumor margin areas of ductal carcinomas were much harder than in tubular carcinoma and micro-carcinoma, respectively (P < 0.05). SWV ROC curve analyses yielded a cut-off value of 3.015 m/s between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma in the central part of lesions, with 83.5% sensitivity and 80% specificity for T0 vs T1-3 staging. Since some features were associated with different breast carcinoma types and stages, ABVS and SWV imaging has the potential to give clues about breast carcinoma differentiation in a non-invasive manner. Copyright © 2016 Elsevier Ltd. All rights reserved.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.

PubMed

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B; Jansen, Sanaz A; Macleod, Kay; Conzen, Suzanne D; Karczmar, Gregory S

2015-01-01

The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25μL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p<0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p<0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma.

PubMed

Blair, Alex B; Zheng, Lei

2017-06-01

The complex interaction between the immune system, the tumor and the microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the resistance of PDA to immunotherapy. To overcome this resistance, combination immunotherapy is being proposed. However, rational combinations that target multiple aspects of the complex anti-tumor immune response are warranted. Novel clinical trials will investigate and optimize the combination immunotherapy for PDA.

Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (PDE4D4), in Determining Prostate Cancer Risk

DTIC Science & Technology

2007-04-01

ductal prostate adenocarcinomas in NBL / Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17h or...Androl 1981;2(6):293–9. 80] Bosland MC, Ford H, Horton L. Induction at high incidence of ductal prostate adenocarcinomas in NBL /Cr and Sprague–Dawley

Examination of Duct Physiology in the Human Mammary Gland

PubMed Central

Mills, Dixie; Gomberawalla, Ameer; Gordon, Eva J.; Tondre, Julie; Nejad, Mitra; Nguyen, Tinh; Pogoda, Janice M.; Rao, Jianyu; Chatterton, Robert; Henning, Susanne; Love, Susan M.

2016-01-01

Background The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. PMID:27073976

Blunt pancreatic trauma: A persistent diagnostic conundrum?

PubMed Central

Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

2016-01-01

Blunt pancreatic trauma is an uncommon injury but has high morbidity and mortality. In modern era of trauma care, pancreatic trauma remains a persistent challenge to radiologists and surgeons alike. Early detection of pancreatic trauma is essential to prevent subsequent complications. However early pancreatic injury is often subtle on computed tomography (CT) and can be missed unless specifically looked for. Signs of pancreatic injury on CT include laceration, transection, bulky pancreas, heterogeneous enhancement, peripancreatic fluid and signs of pancreatitis. Pan-creatic ductal injury is a vital decision-making parameter as ductal injury is an indication for laparotomy. While lacerations involving more than half of pancreatic parenchyma are suggestive of ductal injury on CT, ductal injuries can be directly assessed on magnetic resonance imaging (MRI) or encoscopic retrograde cholangio-pancreatography. Pancreatic trauma also shows temporal evolution with increase in extent of injury with time. Hence early CT scans may underestimate the extent of injures and sequential imaging with CT or MRI is important in pancreatic trauma. Sequential imaging is also needed for successful non-operative management of pancreatic injury. Accurate early detection on initial CT and adopting a multimodality and sequential imaging strategy can improve outcome in pancreatic trauma. PMID:26981225

Net Expression Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Cell PL45 In Vitro and In Vivo

PubMed Central

Li, Baiwen; Wan, Xinjian; Zhu, Qi; Li, Lei; Zeng, Yue; Hu, Duanmin; Qian, Yueqin; Lu, Lungen; Wang, Xingpeng; Meng, Xiangjun

2013-01-01

Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene. PMID:23469073

Endometrial Metastasis from Ductal Breast Carcinoma: A Case Report with Literature Review.

PubMed

Rahmani, Maryam; Nili, Fatemeh; Tabibian, Elnaz

2018-04-27

BACKGROUND There are few reports of breast cancer cases with uterine metastases; among them, myometrium is more frequently involved than endometrium. The majority of breast cancer metastases to endometrium are lobular type, and there have been only 5 reported cases of ductal type since 1984. Here, we describe a new case of invasive ductal carcinoma with metastases to endometrium and isolated presentation of abnormal uterine bleeding, in addition to reviewing the existing literature on other similar cases. CASE REPORT The patient was a 51-year-old Persian woman with no remarkable past medical or family history of cancer, who presented with a 6-month complaint of menorrhagia to our gynecology clinic. Diagnostic studies including trans-vaginal ultrasonography, pathological examination of endometrial curettage specimen, immunohistochemistry findings, and X-plane and magnetic resonance mammography, and breast core-needle biopsy revealed invasive ductal breast carcinoma as the origin of the endometrial metastasis. CONCLUSIONS Abnormal uterine bleeding in a premenopausal patient should alert clinicians to the possibility of secondary as well as primary neoplasms. It is necessary to differentiate a metastatic tumor from a primary one, since the treatment and prognosis are completely different.

Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein Levels in Parathyroid Hyperplasia over Adenoma

PubMed Central

AKPINAR, GURLER; KASAP, MURAT; CANTURK, NUH ZAFER; ZULFIGAROVA, MEHIN; ISLEK, EYLÜL ECE; GULER, SERTAC ATA; SIMSEK, TURGAY; CANTURK, ZEYNEP

2017-01-01

Background/Aim: To unveil the pathophysiology of primary hyperparathyroidism, molecular details of parathyroid hyperplasia and adenoma have to be revealed. Such details will provide the tools necessary for differentiation of these two look-alike diseases. Therefore, in the present study, a comparative proteomic study using postoperative tissue samples from the parathyroid adenoma and parathyroid hyperplasia patients was performed. Materials and Methods: Protein extracts were prepared from tissue samples (n=8 per group). Protein pools were created for each group and subjected to DIGE and conventional 2DE. Following image analysis, spots representing the differentially regulated proteins were excised from the and used for identification via MALDI-TOF/TOF analysis. Results: The identities of 40 differentially-expressed proteins were revealed. Fourteen of these proteins were over-expressed in the hyperplasia while 26 of them were over-expressed in the adenoma. Conclusion: Most proteins found to be over-expressed in the hyperplasia samples were mitochondrial, underlying the importance of the mitochondrial activity as a potential biomarker for differentiation of parathyroid hyperplasia from adenoma. PMID:28446534

Contemporary biological markers of exposure to fluoride.

PubMed

Rugg-Gunn, Andrew John; Villa, Alberto Enrique; Buzalaf, Marília Rabelo Afonso

2011-01-01

Contemporary biological markers assess present, or very recent, exposure to fluoride: fluoride concentrations in blood, bone surface, saliva, milk, sweat and urine have been considered. A number of studies relating fluoride concentration in plasma to fluoride dose have been published, but at present there are insufficient data on plasma fluoride concentrations across various age groups to determine the 'usual' concentrations. Although bone contains 99% of the body burden of fluoride, attention has focused on the bone surface as a potential marker of contemporary fluoride exposure. From rather limited data, the ratio surface-to-interior concentration of fluoride may be preferred to whole bone fluoride concentration. Fluoride concentrations in the parotid and submandibular/sublingual ductal saliva follow the plasma fluoride concentration, although at a lower concentration. At present, there are insufficient data to establish a normal range of fluoride concentrations in ductal saliva as a basis for recommending saliva as a marker of fluoride exposure. Sweat and human milk are unsuitable as markers of fluoride exposure. A proportion of ingested fluoride is excreted in urine. Plots of daily urinary fluoride excretion against total daily fluoride intake suggest that daily urinary fluoride excretion is suitable for predicting fluoride intake for groups of people, but not for individuals. While fluoride concentrations in plasma, saliva and urine have some ability to predict fluoride exposure, present data are insufficient to recommend utilizing fluoride concentrations in these body fluids as biomarkers of contemporary fluoride exposure for individuals. Daily fluoride excretion in urine can be considered a useful biomarker of contemporary fluoride exposure for groups of people, and normal values have been published. Copyright © 2011 S. Karger AG, Basel.

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

PubMed

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma.

PubMed

Joseph, Nancy M; Ferrell, Linda D; Jain, Dhanpat; Torbenson, Michael S; Wu, Tsung-Teh; Yeh, Matthew M; Kakar, Sanjay

2014-01-01

Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloid-associated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant patterns of staining with glutamine synthetase and serum amyloid-associated protein in inflammatory hepatocellular adenoma and focal nodular hyperplasia.

Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age

PubMed Central

2013-01-01

Introduction Endometrial hyperplasia has a high risk for malignant transformation and relapses; existing mini-invasive treatments may lead to irrevocable endometrium destruction. The aims were to analyze receptor systems in endometrial hyperplasia, to evaluate the capabilities of ultrasonography, sonoelastography for diagnosis and treatment control, and to develop treatment algorithm. Materials and methods We included 313 women (20–45 years), assessed into the following: group 1 (n = 112) with glandular cystic hyperplasia, group 2 (n = 98) endometrial polyps, and group 3 (n = 103) atypical hyperplasia; and 82 controls who have undergone hysteroscopy before in vitro fertilization in tubal origin infertility were also included. Patients underwent clinical examination, transvaginal ultrasound, immunohistochemical study, and hormonal therapy/hysteroresectoscopy. Results In patients with glandular hyperplasia, we registered increase of endometrium estrogen receptors (75.6% in the epithelium and 30.9% in the stroma; in controls, 43.3% and 29.6%, respectively); in polyps, there was a significant estrogen receptor increase in the stroma (48.2% vs 29.6% in controls), and in atypical hyperplasia, progesterone receptors significantly increased in the stroma. Ki-67 increased (40% to 50%) in the epithelium without changes in the stroma. Ultrasound has a sensitivity of 96% and a specificity of 85% for early detection of endometrial pathology and prediction outcome of intervention, and sonoelastography has a sensitivity of 91% and a specificity of 83% for polyp diagnosis. Personalized treatment was effective in 88.8%, relapse was diagnosed in 11.2% after 6 months, and conservative treatment of atypical hyperplasia was effective in 45%: in 25.8%, ablative hysteroresectoscopy was performed, while in 22.6% with comorbidities, hystero/oophorectomies were performed. Conclusions The evaluation of receptor status with ultrasound data in patients with endometrial hyperplasia allows for a clear definition of the treatment policy, avoidance of relapse, treatment optimization, and observation of such patients. PMID:24314145

Ductal carcinoma of the breast in the pacemaker generator's pocket.

PubMed

Zonca, P; Herokova, J; Cambal, M; Jacobi, C A

2009-01-01

Authors present a case of a 78-year-old female patient with invasive ductal adenocarcinoma in the pacemaker, s pocket. A decubitus-like tumor had developed in this place, and has been missinterpretated as a benign lesion for 5 months. Diagnosis was done with a time delay. An excisional biopsy revealed annvasive ductal adenocarcinoma. The first step was the implantation of a new pacemaker generator performed on the opposite side. The second step was a modified radical mastectomy, according to Madden, and the removal of the originally implanted pacemaker generator. Radiotherapy and hormonal adjuvant therapy were applied after surgery. The patient was followed-up at an out-patient clinic, and died 25 months after diagnosis because of generalization of the disease (Fig. 2, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

Lymphangioma circumscriptum, angiokeratoma, or superficial vascular ectasia with epithelial hyperplasia?

PubMed

Katsoulas, Nikolaos; Tosios, Konstantinos I; Argyris, Prokopios; Koutlas, Ioannis G; Sklavounou, Alexandra

2014-08-01

We report a case of lymphangioma circumscriptum (cavernous lymphangioma with epithelial hyperplasia) in a 12-year-old girl, presenting as a papillary tumor on the right dorsal side of her tongue. Microscopic examination found cavernous vascular channels lined by a single layer of CD31(+), podoplanin-positive, CD34(-) endothelial cells that occupied the papillary lamina propria and were accompanied by epithelial hyperplasia. A review of the literature on oral vascular tumors with epithelial hyperplasia, namely, lymphangioma circumscriptum and angiokeratoma, provided information that draws into question the use of these terms. Copyright © 2014 Elsevier Inc. All rights reserved.

A Recurrence of Bilateral Diffuse Sclerosing Lobular Hyperplasia of Breast: A Case Report.

PubMed

Elfituri, Osama; Sonawane, Snehal; Xu, Haoliang; Warso, Michael A; Wiley, Elizabeth

2017-12-01

Mammary sclerosing lobular hyperplasia is an uncommon benign fibroproliferative lesion of adolescent and young women, often of African American heritage with an incidence of ~3%. Patients generally complain of a palpable, painless, or slightly tender and well-defined lump in breast. Very rarely, this lesion may be bilateral and diffuse. The definitive diagnosis of sclerosing lobular hyperplasia requires histopathologic evaluation. Here, we describe a case of diffuse sclerosing lobular hyperplasia in a 29-year-old African American woman that required bilateral mastectomy and recurred bilaterally requiring second resections. This appears to be the first report of this phenomenon.

Angiolymphoid hyperplasia with eosinophilia versus Kimura's disease: a case report and a clinical and histopathological comparison*

PubMed Central

de Bastos, Julien Totti; da Rocha, Camila Roos Mariano; Silva, Priscila Mara Chaves e; de Freitas, Bruno Messias Pires; Cassia, Flávia de Freire; Avelleira, João Carlos Regazzi

2017-01-01

Angiolymphoid hyperplasia with eosinophilia is a rare and benign vascular tumor whose etiology remains uncertain. It clinically presents itself by angiomatous papules or nodules located on the head and neck. Many controversies in the literature are found in relation to angiolymphoid hyperplasia with eosinophilia and Kimura's disease - its main differential diagnosis - due to their clinical and histopathological similarities. However, currently, most studies agree that they are distinct diseases. The present case illustrates a characteristic description of angiolymphoid hyperplasia with eosinophilia and also highlights the main differences with Kimura's disease. PMID:29186256

Sebaceous hyperplasia of the vulva: a series of cases reporting no association with the Muir-Torre syndrome.

PubMed

Roma, Andres A; Barry, Jessica; Pai, Rish K; Billings, Steven D

2014-07-01

Sebaceous gland hyperplasia is a common skin condition, very rarely reported in the female genital region. We present 13 cases from 12 patients, the first case series of sebaceous gland hyperplasia of the vulva. Differences in age at presentation and clinical presentation compared with classic sebaceous gland hyperplasia from the head and neck region were noted. Also, it was rarely included in the clinical differential diagnosis. Immunohistochemical studies to determine any possible association with the Muir-Torre syndrome were performed and mismatch repair protein loss was not identified.

Hypogammaglobulinemia associated with nodular lymphoid hyperplasia of the intestine and pernicious anaemia.

PubMed

Ouakaa-Kchaou, Asma; Trad, Dorra; Boussourra, Houda; Bibani, Norsaf; Elloumi, Héla; Kochlef, Asma; Gargouri, Dalila; Kharrat, Jamel

2015-11-01

Nodular lymphoid hyperplasia of the gastrointestinal tract, recurrent acute pulmonary infections and autoimmune disease are well-recognized complications of common variable immunodeficiency. We aimed to focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid and hyperplasia of the gastrointestinal tract coexisting with hypogammaglobulinemia. We report the case of nodular lymphoid hyperplasia associated with pernicious anaemia in a young man with hypogammaglobulinemia and a long history of pulmonary infections. The considerable point was a mismatch primary clinical diagnosis of familial adenomatous polyposis, due to prominent polyplike endoscopic appearance of the lesions throughout the digestive tract.

A Study of Using Massage Therapy Accompanied with Stretching Exercise for Rehabilitation of Mammary Gland Hyperplasia.

PubMed

Lv, Pin; Chong, Yuping; Zou, Huagang; Chen, Xiangxian

2016-01-01

To apply massage therapy accompanied with stretching exercises for treatment of mammary gland hyperplasia, evaluate the clinical outcome in patients, and estimate the therapy as a novel treatment method for mammary hyperplasia. 28 adult female patients were selected and treated with massage therapy and stretching exercises focusing on skeleton muscles of chest, abdomen, and axilla. The mammary gland oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb) levels were detected before and after treatment after 15, 30, and 45 days. In this cohort, pretreatment OxyHb (mean ± SD) is 1.32 ± 0.14 (medium-high), and DeoxyHb is 0.87 ± 0.13 (normal). All patients were clinically diagnosed with benign mammary gland hyperplasia and mastitis. The posttreatment OxyHb levels are 1.23 ± 0.09 (normal-medium, 15-day), 1.16 ± 0.08 (normal, 30-day), and 1.05 ± 0.04 (normal, 45-day), and DeoxyHb levels are 0.90 ± 0.11 (normal, 15-day), 0.94 ± 0.18 (normal, 30-day), and 0.98 ± 0.12 (normal, 45-day). Patients were diagnosed with decreased hyperplasia 15 and 30 days after treatment and with no symptom of hyperplasia in mammary gland 45 days after treatment. Mammary gland hyperplasia is closely correlated with pathological changes of skeletal muscles and could be significantly improved by massage therapy and stretching exercises targeting neighboring skeletal muscles.

Role of the Renin–Angiotensin System in the Pathogenesis of Intimal Hyperplasia: Therapeutic Potential for Prevention of Vein Graft Failure?

PubMed Central

Osgood, Michael J.; Harrison, David G.; Sexton, Kevin W.; Hocking, Kyle M.; Voskresensky, Igor V.; Komalavilas, Padmini; Cheung-Flynn, Joyce; Guzman, Raul J.; Brophy, Colleen M.

2014-01-01

The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The rennin–angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin–angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the rennin–angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the rennin–angiotensin system in the pathogenesis of intimal hyperplasia. PMID:22445245

Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia.

PubMed

Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

2016-01-01

Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76-39.71%); group C, 16.21% (95% CI, 13.36-19.05%); and group A, 21.12% (95% CI, 17.26-25.01%); P < 0.0001. We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia

PubMed Central

Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

2016-01-01

Objective Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol. PMID:27849301

Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

PubMed Central

Arima, Kazuhiko; Ohta, Shoichiro; Takagi, Atsushi; Shiraishi, Hiroshi; Masuoka, Miho; Ontsuka, Kanako; Suto, Hajime; Suzuki, Shoichi; Yamamoto, Ken-ichi; Ogawa, Masahiro; Simmons, Olga; Yamaguchi, Yukie; Toda, Shuji; Aihara, Michiko; Conway, Simon J.; Ikeda, Shigaku; Izuhara, Kenji

2016-01-01

Background Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis. Methods To examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin’s role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ). Results Periostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, –22, or –23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells. Conclusions Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis. PMID:25572557

Ibuprofen induces reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA uptake in severe epithelial breast hyperplasia without atypia.

PubMed

Papantoniou, Vassilios; Tsaroucha, Angeliki; Valsamaki, Pipitsa; Tsiouris, Spyridon; Sotiropoulou, Evangelia; Karianos, Theodore; Marinopoulos, Spyridon; Fothiadaki, Athina; Sotiropoulou, Maria; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Dimitrakakis, Konstantinos; Antsaklis, Aris

2010-10-01

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n  =  4) and without atypia (n  =  4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p  =  .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p  =  .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

Progenitor potential of nkx6.1-expressing cells throughout zebrafish life and during beta cell regeneration.

PubMed

Ghaye, Aurélie P; Bergemann, David; Tarifeño-Saldivia, Estefania; Flasse, Lydie C; Von Berg, Virginie; Peers, Bernard; Voz, Marianne L; Manfroid, Isabelle

2015-09-02

In contrast to mammals, the zebrafish has the remarkable capacity to regenerate its pancreatic beta cells very efficiently. Understanding the mechanisms of regeneration in the zebrafish and the differences with mammals will be fundamental to discovering molecules able to stimulate the regeneration process in mammals. To identify the pancreatic cells able to give rise to new beta cells in the zebrafish, we generated new transgenic lines allowing the tracing of multipotent pancreatic progenitors and endocrine precursors. Using novel bacterial artificial chromosome transgenic nkx6.1 and ascl1b reporter lines, we established that nkx6.1-positive cells give rise to all the pancreatic cell types and ascl1b-positive cells give rise to all the endocrine cell types in the zebrafish embryo. These two genes are initially co-expressed in the pancreatic primordium and their domains segregate, not as a result of mutual repression, but through the opposite effects of Notch signaling, maintaining nkx6.1 expression while repressing ascl1b in progenitors. In the adult zebrafish, nkx6.1 expression persists exclusively in the ductal tree at the tip of which its expression coincides with Notch active signaling in centroacinar/terminal end duct cells. Tracing these cells reveals that they are able to differentiate into other ductal cells and into insulin-expressing cells in normal (non-diabetic) animals. This capacity of ductal cells to generate endocrine cells is supported by the detection of ascl1b in the nkx6.1:GFP ductal cell transcriptome. This transcriptome also reveals, besides actors of the Notch and Wnt pathways, several novel markers such as id2a. Finally, we show that beta cell ablation in the adult zebrafish triggers proliferation of ductal cells and their differentiation into insulin-expressing cells. We have shown that, in the zebrafish embryo, nkx6.1+ cells are bona fide multipotent pancreatic progenitors, while ascl1b+ cells represent committed endocrine precursors. In contrast to the mouse, pancreatic progenitor markers nkx6.1 and pdx1 continue to be expressed in adult ductal cells, a subset of which we show are still able to proliferate and undergo ductal and endocrine differentiation, providing robust evidence of the existence of pancreatic progenitor/stem cells in the adult zebrafish. Our findings support the hypothesis that nkx6.1+ pancreatic progenitors contribute to beta cell regeneration. Further characterization of these cells will open up new perspectives for anti-diabetic therapies.

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate.

PubMed

MacDougall, Lori D

2003-03-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed.

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

PubMed Central

MacDougall, Lori D.

2003-01-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia.

PubMed

Saad, Amin F; Ford, Kenneth L; Deprisco, Gregory; Smerud, Michael J

2013-07-01

Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed.

Comparison of 99mTc-MDP SPECT qualitative vs quantitative results in patients with suspected condylar hyperplasia.

PubMed

López Buitrago, D F; Ruiz Botero, J; Corral, C M; Carmona, A R; Sabogal, A

To compare qualitative vs quantitative results of Single Photon Emission Computerised Tomography (SPECT), calculated from percentage of 99m Tc-MDP (methylene diphosphonate) uptake, in condyles of patients with a presumptive clinical diagnosis of condylar hyperplasia. A retrospective, descriptive study was conducted on the 99m Tc-MDP SPECT bone scintigraphy reports from 51 patients, with clinical impression of facial asymmetry related to condylar hyperplasia referred by their specialist in orthodontics or maxillofacial surgery, to a nuclear medicine department in order to take this type of test. Quantitative data from 99m Tc-MDP condylar uptake of each were obtained and compared with qualitative image interpretation reported by a nuclear medicine expert. The concordances between the 51 qualitative and quantitative reports results was established. The total sample included 32 women (63%) and 19 men (37%). The patient age range was 13-45 years (21±8 years). According to qualitative reports, 19 patients were positive for right side condylar hyperplasia, 12 for left side condylar hyperplasia, with 8 bilateral, and 12 negative. The quantitative reports diagnosed 16 positives for right side condylar hyperplasia, 10 for left side condylar hyperplasia, and 25 negatives. Nuclear medicine images are an important diagnostic tool, but the qualitative interpretation of the images is not as reliable as the quantitative calculation. The agreement between the two types of report is low (39.2%, Kappa=0.13; P>.2). The main limitation of quantitative reports is that they do not register bilateral condylar hyperplasia cases. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

PubMed

Kijani, Siavash; Vázquez, Ana Maria; Levin, Malin; Borén, Jan; Fogelstrand, Per

2017-07-01

Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

ClinicalTrials.gov

2017-06-07

Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma

PubMed Central

Beatty, Gregory L

2014-01-01

Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells is under investigation as an approach to restore productive T cell immunosurveillance in patients with pancreatic ductal adenocarcinoma. Early findings demonstrate safety of this cell-based therapy and the capacity of CAR-expressing T cells to mediate anti-tumor activity as well as induce endogeneous antitumoral immune responses. PMID:25050204

DIE-RNA: A Reproducible Strategy for the Digestion of Normal and Injured Pancreas, Isolation of Pancreatic Cells from Genetically Engineered Mouse Models and Extraction of High Quality RNA

PubMed Central

Assi, Mohamad; Dauguet, Nicolas; Jacquemin, Patrick

2018-01-01

The isolation of ribonucleic acid (RNA) suitable for gene expression studies is challenging in the pancreas, due to its high ribonuclease activity. This is even more complicated during pancreatitis, a condition associated with inflammation and fibrosis. Our aim was to implement a time-effective and reproducible protocol to isolate high quality RNA from specific pancreatic cell subtypes, in normal and inflammatory conditions. We used two genetically engineered mouse models (GEMM), Ela-CreER/YFP and Sox9-CreER/YFP, to isolate acinar and ductal cells, respectively. To induce pancreatitis, mice received a caerulein treatment (125 μg/kg) for 8 and 72 h. We alternatively used EGTA and calcium buffers that contain collagenase P (0.6 mg/mL) to rapidly digest the pancreas into individual cells. Most of the cells from normal and injured pancreas were single-dissociated, exhibited a round morphology and did not incorporate trypan blue dye. Cell suspensions from Ela- and Sox9-CreER/YFP pancreas were then sorted by flow cytometry to isolate the YFP-positive acinar and ductal cells, respectively. Sorted cells kept a round shape and emitted fluorescence detected by the 38 HE green fluorescence filter. RNA was isolated by column-based purification approach. The RNA integrity number (RIN) was high in sorted acinar cell fractions treated with or without caerulein (8.6 ± 0.17 and 8.4 ± 0.09, respectively), compared to the whole pancreas fraction (4.8 ± 1.1). Given the low number of sorted ductal cells, the RIN value was slightly lower compared to acini (7.4 ± 0.4). Quantitative-PCR experiments indicated that sorted acinar and ductal cells express the specific acinar and ductal markers, respectively. Additionally, RNA preparations from caerulein-treated acinar cells were free from significant contamination with immune cell RNA. We thus validated the DIE (Digestion, Isolation, and Extraction)-RNA tool as a reproducible and efficient protocol to isolate pure acinar and ductal cells in vivo and to extract high quality RNA from these cells. PMID:29535635

DIE-RNA: A Reproducible Strategy for the Digestion of Normal and Injured Pancreas, Isolation of Pancreatic Cells from Genetically Engineered Mouse Models and Extraction of High Quality RNA.

PubMed

Assi, Mohamad; Dauguet, Nicolas; Jacquemin, Patrick

2018-01-01

The isolation of ribonucleic acid (RNA) suitable for gene expression studies is challenging in the pancreas, due to its high ribonuclease activity. This is even more complicated during pancreatitis, a condition associated with inflammation and fibrosis. Our aim was to implement a time-effective and reproducible protocol to isolate high quality RNA from specific pancreatic cell subtypes, in normal and inflammatory conditions. We used two genetically engineered mouse models (GEMM), Ela-CreER/YFP and Sox9-CreER/YFP, to isolate acinar and ductal cells, respectively. To induce pancreatitis, mice received a caerulein treatment (125 μg/kg) for 8 and 72 h. We alternatively used EGTA and calcium buffers that contain collagenase P (0.6 mg/mL) to rapidly digest the pancreas into individual cells. Most of the cells from normal and injured pancreas were single-dissociated, exhibited a round morphology and did not incorporate trypan blue dye. Cell suspensions from Ela- and Sox9-CreER/YFP pancreas were then sorted by flow cytometry to isolate the YFP-positive acinar and ductal cells, respectively. Sorted cells kept a round shape and emitted fluorescence detected by the 38 HE green fluorescence filter. RNA was isolated by column-based purification approach. The RNA integrity number (RIN) was high in sorted acinar cell fractions treated with or without caerulein (8.6 ± 0.17 and 8.4 ± 0.09, respectively), compared to the whole pancreas fraction (4.8 ± 1.1). Given the low number of sorted ductal cells, the RIN value was slightly lower compared to acini (7.4 ± 0.4). Quantitative-PCR experiments indicated that sorted acinar and ductal cells express the specific acinar and ductal markers, respectively. Additionally, RNA preparations from caerulein-treated acinar cells were free from significant contamination with immune cell RNA. We thus validated the DIE (Digestion, Isolation, and Extraction)-RNA tool as a reproducible and efficient protocol to isolate pure acinar and ductal cells in vivo and to extract high quality RNA from these cells.

Mixed ductal‐lobular carcinomas: evidence for progression from ductal to lobular morphology

PubMed Central

McCart Reed, Amy E; Kutasovic, Jamie R; Nones, Katia; Saunus, Jodi M; Da Silva, Leonard; Newell, Felicity; Kazakoff, Stephen; Melville, Lewis; Jayanthan, Janani; Vargas, Ana Cristina; Reid, Lynne E; Beesley, Jonathan; Chen, Xiao Qing; Patch, Anne-Marie; Clouston, David; Porter, Alan; Evans, Elizabeth; Pearson, John V; Chenevix‐Trench, Georgia; Cummings, Margaret C; Waddell, Nicola; Lakhani, Sunil R

2018-01-01

Abstract Mixed ductal–lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent ‘collision’ of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E‐cadherin–catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E‐cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E‐cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E‐cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E‐cadherin. The mechanisms driving the phenotypic change may involve E‐cadherin–catenin complex deregulation, but are yet to be fully elucidated, as there is significant intertumoural heterogeneity, and each case may have a unique molecular mechanism. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:29344954

[Surgical treatment of pain in chronic pancreatitis].

PubMed

Stefanović, Dejan; Knezević, Srbislav; Djordjević, Zoran; Kerkez, Mirko; Bulajić, Predrag; Marković, Ljiljana

2006-01-01

The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. All patients of Group I (30) underwent latero-lateral pancreaticojejunal--Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W) was done in 6 patients, pylorus preserving Whipple (PPW) in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP) was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanlioglu, Ahter D.; Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya; Korcum, Aylin F.

2007-11-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, thismore » study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.« less

Sonographic findings of high-grade and non-high-grade ductal carcinoma in situ of the breast.

PubMed

Park, Ji-Sung; Park, Young-Mi; Kim, Eun-Kyung; Kim, Suk-Jung; Han, Sang-Suk; Lee, Sun-Joo; In, Hyun-Sin; Ryu, Ji-Hwa

2010-12-01

The purpose of this study was to differentiate between high-grade and non-high-grade ductal carcinoma in situ (DCIS) of the breast on sonography. From October 2003 to August 2009, 76 DCIS lesions in 73 women who underwent sonography and mammography were included in this study. Lesions were confirmed by mastectomy, breast-conserving surgery, or surgical biopsy. Images were analyzed by 2 radiologists with consensus and were correlated with histologic grades. Of the 76 lesions, 44 were classified as high--grade and 32 as non-high-grade DCIS. Fifty-seven lesions (75.0%) were identified on sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal changes in 4, and architectural distortion in 3. All cases with false-negative findings on sonography (n = 19) showed microcalcifications on mammography. On sonography, masses were more frequently found in non-high-grade (62.5%) than high-grade DCIS (22.7%; P < .01). No significant difference was seen in the sonographic features of masses between high-grade and non-high-grade DCIS. Microcalcifications were more common in high-grade (43.2%) than non-high-grade (3.1%) DCIS (P = .02). Most sonographically visible microcalcifications had associated findings such as ductal changes (n = 11), a mass (n = 7), or a hypoechoic area (n = 5). The detection rate of microcalcifications on sonography was higher in high-grade (62.9%) than non-high-grade DCIS (25.0%; P = .023). Microcalcifications with associated ductal changes (11 of 31 [35.5%]) were the most common sonographic findings in high-grade DCIS. An irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26 [50.0%]) was the most frequent finding in non-high-grade DCIS.

Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia

PubMed Central

Ford, Kenneth L.; dePrisco, Gregory; Smerud, Michael J.

2013-01-01

Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed. PMID:23814386

Intracytoplasmic Crystalline Inclusions in the Hepatocytes of an Antelope

DTIC Science & Technology

2010-01-01

fine basophilic granules with hematoxylin and eosin stain (Figure 2(a)). Periportal areas had moderately increased fibrous connective tissue with marked...biliary hyperplasia , mild oval cell hyperplasia , and moderate infiltrates of predominant lymphocytes and plasma cells with occasional neutrophils...cholangiohepatitis, bridging portal fibrosis and biliary hyperplasia . There was no evidence of hepatocellular Report Documentation Page Form ApprovedOMB No. 0704

Covalent modification of pericardial patches for sustained rapamycin delivery inhibits venous neointimal hyperplasia

PubMed Central

Bai, Hualong; Lee, Jung Seok; Chen, Elizabeth; Wang, Mo; Xing, Ying; Fahmy, Tarek M.; Dardik, Alan

2017-01-01

Prosthetic grafts and patches are commonly used in cardiovascular surgery, however neointimal hyperplasia remains a significant concern, especially under low flow conditions. We hypothesized that delivery of rapamycin from nanoparticles (NP) covalently attached to patches allows sustained site-specific delivery of therapeutic agents targeted to inhibit localized neointimal hyperplasia. NP were covalently linked to pericardial patches using EDC/NHS chemistry and could deliver at least 360 ng rapamycin per patch without detectable rapamycin in serum; nanoparticles were detectable in the liver, kidney and spleen but no other sites within 24 hours. In a rat venous patch angioplasty model, control patches developed robust neointimal hyperplasia on the patch luminal surface characterized by Eph-B4-positive endothelium and underlying SMC and infiltrating cells such as macrophages and leukocytes. Patches delivering rapamycin developed less neointimal hyperplasia, less smooth muscle cell proliferation, and had fewer infiltrating cells but retained endothelialization. NP covalently linked to pericardial patches are a novel composite delivery system that allows sustained site-specific delivery of therapeutics; NP delivering rapamycin inhibit patch neointimal hyperplasia. NP linked to patches may represent a next generation of tissue engineered cardiovascular implants. PMID:28071663

Epidermal psoriasiform hyperplasia, an unrecognized sign of folliculitis decalvans: A histological study of 26 patients.

PubMed

Matard, Bruno; Cavelier-Balloy, Benedicte; Reygagne, Pascal

2017-04-01

Follicular hyperkeratosis along with hyperplasia of the follicular and interfollicular epithelia are major histopathological characteristics of hidradenitis suppurativa (HS). The presence of an occasional thickening of lesional skin in some folliculitis decalvans (FD) patients and histological similarities between FD and HS led us to look for epidermal hyperplasia and follicular hyperkeratosis in FD patients. We performed a retrospective histological analysis of 26 patients with FD. We sought to find out whether the presence of hyperplasia of the interfollicular epidermis and of the follicular epithelia could be verified in FD, with reference to the work of von Laffert et al. concerning HS. The main quantitative and qualitative data were: follicular hyperkeratosis (77%), hyperplasia of the interfollicular epidermis (92%) with a psoriasiform aspect (88%), atrophy of the follicular epithelia (85%), plasma cells in infiltrate (92%) in large quantities (42%), follicular microcysts (60%), atrophy of the sebaceous glands (85%) and polytrichia (54%). Epidermal hyperplasia, sometimes psoriasiform and follicular microcysts, are significant histological signs of FD, which have been ignored until now although they seem very common. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Covalent modification of pericardial patches for sustained rapamycin delivery inhibits venous neointimal hyperplasia

NASA Astrophysics Data System (ADS)

Bai, Hualong; Lee, Jung Seok; Chen, Elizabeth; Wang, Mo; Xing, Ying; Fahmy, Tarek M.; Dardik, Alan

2017-01-01

Prosthetic grafts and patches are commonly used in cardiovascular surgery, however neointimal hyperplasia remains a significant concern, especially under low flow conditions. We hypothesized that delivery of rapamycin from nanoparticles (NP) covalently attached to patches allows sustained site-specific delivery of therapeutic agents targeted to inhibit localized neointimal hyperplasia. NP were covalently linked to pericardial patches using EDC/NHS chemistry and could deliver at least 360 ng rapamycin per patch without detectable rapamycin in serum; nanoparticles were detectable in the liver, kidney and spleen but no other sites within 24 hours. In a rat venous patch angioplasty model, control patches developed robust neointimal hyperplasia on the patch luminal surface characterized by Eph-B4-positive endothelium and underlying SMC and infiltrating cells such as macrophages and leukocytes. Patches delivering rapamycin developed less neointimal hyperplasia, less smooth muscle cell proliferation, and had fewer infiltrating cells but retained endothelialization. NP covalently linked to pericardial patches are a novel composite delivery system that allows sustained site-specific delivery of therapeutics; NP delivering rapamycin inhibit patch neointimal hyperplasia. NP linked to patches may represent a next generation of tissue engineered cardiovascular implants.

Cellular automaton simulation examining progenitor hierarchy structure effects on mammary ductal carcinoma in situ.

PubMed

Bankhead, Armand; Magnuson, Nancy S; Heckendorn, Robert B

2007-06-07

A computer simulation is used to model ductal carcinoma in situ, a form of non-invasive breast cancer. The simulation uses known histological morphology, cell types, and stochastic cell proliferation to evolve tumorous growth within a duct. The ductal simulation is based on a hybrid cellular automaton design using genetic rules to determine each cell's behavior. The genetic rules are a mutable abstraction that demonstrate genetic heterogeneity in a population. Our goal was to examine the role (if any) that recently discovered mammary stem cell hierarchies play in genetic heterogeneity, DCIS initiation and aggressiveness. Results show that simpler progenitor hierarchies result in greater genetic heterogeneity and evolve DCIS significantly faster. However, the more complex progenitor hierarchy structure was able to sustain the rapid reproduction of a cancer cell population for longer periods of time.

Effect of Nitric Oxide on Neointimal Hyperplasia based on Sex and Hormone Status

PubMed Central

Hogg, Melissa E.; Varu, Vinit N.; Vavra, Ashley K.; Popowich, Daniel A.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Saavedra, Joseph E.; Keefer, Larry K.; Kibbe, Melina R.

2011-01-01

Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have only been performed in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete media, male VSMC proliferated at greater rates than female VSMC. In hormone-deplete media, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male versus female VSMC. These findings correlated with greater G0/G1 cell cycle arrest and changes in cell cycle protein expression in male versus female VSMC following exposure to NO. Next, the rat carotid artery injury model was performed to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males versus females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in both sexes in castrated animals. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males than females and in hormonally-intact compared to castrated rats, indicating that the effect of NO in the vasculature may be sex- and hormone-dependent. PMID:21256959

Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device.

PubMed

Pal, Navdeep; Broaddus, Russell R; Urbauer, Diana L; Balakrishnan, Nyla; Milbourne, Andrea; Schmeler, Kathleen M; Meyer, Larissa A; Soliman, Pamela T; Lu, Karen H; Ramirez, Pedro T; Ramondetta, Lois; Bodurka, Diane C; Westin, Shannon N

2018-01-01

To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer. This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined. Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04). Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

Treatment of patent ductus arteriosus by the use of an Amplatz canine ductal occluder device

PubMed Central

White, Pam

2009-01-01

A 7-month-old female, spayed border collie was referred to the Ontario Veterinary College due to a continuous murmur noted by the referring veterinarian prior to ovariohysterectomy. Auscultation confirmed a grade VI/VI continuous murmur. An echocardiogram confirmed patent ductus arteriosus (PDA). An Amplatz canine ductal occluder device was successfully placed for occlusion of blood flow though the ductus. PMID:19436449

Manipulation of NF-KappaBetta Activity in the Macrophage Lineage as a Novel Therapeutic Approach

DTIC Science & Technology

2007-05-01

Sadikot, J. W. Christman, and T. S. Blackwell. 2003. Bioluminescent detection of endotoxin effects on HIV-1 LTR-driven transcription in vivo. J...differences in proliferation rates, expression of downstream gene expression and effects mediated by altered macrophages on associated epithelial...kappaB activity within macrophages has significant effects on mammary ductal development. 15. SUBJECT TERMS NF-kappaB, macrophages, mammary ductal

Enterocolic lymphocytic phlebitis: clinicopathologic features and review of the literature.

PubMed

Ngo, Nyethane; Chang, Fuju

2007-07-01

Enterocolic lymphocytic phlebitis (ELP) is a recently described entity and is of unknown etiology and pathogenesis. It is characterized by phlebitis of the bowel wall and mesentery, without arterial involvement or evidence of systemic vasculitis. The clinical presentation of ELP is varied, but it most commonly manifests with signs of an acute abdomen. Clinical, radiologic, and endoscopic findings are often conflicting and misdiagnosis is common as venous thrombosis is not suspected. The diagnosis of ELP is obtained histologically. There is a spectrum of histologic features associated with ELP, which includes lymphocytic phlebitis, necrotizing phlebitis, granulomatous phlebitis, and myointimal hyperplasia. Other features include venous thrombi and acute ischemic changes of the intestine. Surgical resection of the affected bowel is usually curative and recurrences are rare. The clinical and histopathologic features of ELP are reviewed.

Infrequent Loss of Luminal Differentiation in Ductal Breast Cancer Metastasis

PubMed Central

Calvo, Julia; Sánchez-Cid, Lourdes; Muñoz, Montserrat; Lozano, Juan José; Thomson, Timothy M.; Fernández, Pedro L.

2013-01-01

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. PMID:24205108

Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats.

PubMed

LeSagE, G; Alvaro, D; Benedetti, A; Glaser, S; Marucci, L; Baiocchi, L; Eisel, W; Caligiuri, A; Phinizy, J L; Rodgers, R; Francis, H; Alpini, G

1999-07-01

To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats). After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels. Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin. Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.

The RhoGEF Net1 Is Required for Normal Mammary Gland Development

PubMed Central

Zuo, Yan; Berdeaux, Rebecca

2014-01-01

Neuroepithelial transforming gene 1 (Net1) is a RhoA subfamily-specific guanine nucleotide exchange factor that is overexpressed in human breast cancer and is required for breast cancer cell migration and invasion. However, the role of Net1 in normal mammary gland development or function has never been assessed. To understand the role of Net1 in the mammary gland, we have created a conditional Net1 knockout mouse model. Whole-body deletion of Net1 results in delayed mammary gland development during puberty characterized by slowed of ductal extension and reduced ductal branching. Epithelial cells within the developing ducts show reduced proliferation that is accompanied by diminished estrogen receptor-α expression and activity. Net1-deficient mammary glands also exhibit reduced phosphorylation of regulatory subunits of myosin light chain and myosin light-chain phosphatase, indicating that RhoA-dependent actomyosin contraction is compromised. Net1 deficiency also leads to disorganization of myoepithelial and ductal epithelial cells and increased periductal collagen deposition. Mammary epithelial cell transplantation experiments indicate that reduced ductal branching and disorganization are cell autonomous. These data identify for the first time a role for NET1 in vivo and indicate that NET1 expression is essential for the proliferation and differentiation of mammary epithelial cells in the developing mammary gland. PMID:25321414

Management of intraductal papilloma without atypia of the breast diagnosed on core biopsy: Size and sampling matter.

PubMed

Symbol, Brittany; Ricci, Andrew

2018-04-23

Due to the potential for atypia (atypical ductal or lobular hyperplasia) or carcinoma (in situ or invasive) on excision, aggressive reflex surgical excision protocols following core biopsy diagnosis of papillary lesions of the breast (ie, intraductal papilloma) are commonplace. Concepts in risk stratification, including radiologic-pathologic correlation, are emerging in an effort to curb unnecessary surgeries. To this end, we examined all excised intraductal papillomas diagnosed at our institution from 2010-2015 (N = 336) and found an overall atypia rate of 20%. To investigate further, we stratified all excised papillomas according to total lesion size (range = 1-40 mm) and found that the atypia rate for lesions ≤1.2 cm (16% with atypia) was statistically significantly lower (P = .008) than the atypia rate for lesions >1.2 cm (36% with atypia). To explore to effects of radiologic-pathologic correlation on the ability of the core biopsy to accurately predict nonatypical lesions we assessed thirteen consecutive paired nonatypical core biopsy/follow-up surgical excision specimens for the percent of the total lesion (on imaging) sampled by the core biopsy (measured histologically). None of the thirteen paired specimens showed upgrade on excision (0/13); the percent of total lesion sampled by biopsy in this cohort averaged 59%. We propose that in the absence of discordant clinical/radiological findings, small lesions (≤1.2 cm) with radiologic-pathologic concordance (>50% sampling of total lesion by core biopsy) may safely forego surgery for close clinical and radiographic follow-up. © 2018 Wiley Periodicals, Inc.

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

PubMed

Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

2009-10-10

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

Immunohistochemical study of calretinin in normal skin and cutaneous adnexal proliferations.

PubMed

González-Guerra, Elena; Kutzner, Heinz; Rutten, Arno; Requena, Luis

2012-07-01

Calretinin is a calcium-binding protein member of the EF-hand family. The presence of calretinin has been demonstrated in certain stages of the cellular cycle in a wide variety of normal and neoplastic tissues. The main aims of our study were (1) to investigate what structures of the normal skin and cutaneous adnexal proliferations express immunoreactivity for calretinin and (2) to determine the value of immunohistochemical expression for calretinin as a marker for follicular, sebaceous, apocrine, and eccrine differentiation in cutaneous adnexal proliferations. We studied 139 biopsy specimens, including 10 cases of normal skin of different locations and 129 benign and malignant cutaneous adnexal proliferations. In normal skin, we found that calretinin is expressed in the innermost cell layer of the outer root sheath in anagen hair follicle, in both the duct and sebolemma of the sebaceous gland, in the secretory portion of eccrine glands, and in mast cells of the stroma. In cutaneous adnexal proliferations, we found strong immunoreactivity for calretinin in tricholemmal cysts, tricholemmomas/inverted follicular keratoses, tumors of follicular infundibulum, and in some basal cell carcinomas. Focal positivity was also seen in trichoadenomas, trichoblastomas/trichoepitheliomas, pilomatricomas, proliferating tricholemmal tumors, pilar sheath acanthomas, trichofolliculomas, follicular hybrid cysts, cutaneous mixed tumors, steatocystomas, sebaceous hyperplasias, and sebaceomas. These results demonstrate that immunohistochemical study for calretinin may be helpful to identify the innermost cell layer of the outer root sheath in anagen hair follicle and the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.

Preoperative risk assessment among women undergoing bilateral prophylactic mastectomy for cancer risk reduction.

PubMed

Rueth, Natasha M; McMahon, Melissa; Arrington, Amanda K; Swenson, Karen; Leach, Joseph; Tuttle, Todd M

2011-09-01

Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. Our objective was to determine the prevalence of BRCA testing among women undergoing bilateral prophylactic mastectomy (BPM) and to review the characteristics of women who choose BPM within a metropolitan setting. We retrospectively reviewed records of women who underwent BPM in the absence of cancer within 2 health care systems that included 5 metropolitan hospitals. Women with invasive carcinoma or ductal carcinoma in situ (DCIS) were excluded; neither lobular carcinoma in situ (LCIS) nor atypical hyperplasia (AH) were exclusion criteria. We collected demographic information and preoperative screening and risk assessment, BRCA testing, reconstruction, and associated cancer risk-reducing surgery data. We compared women who underwent BRCA testing to those not tested. From January 2002 to July 2009, a total of 71 BPMs were performed. Only 25 women (35.2%) had preoperative BRCA testing; 88% had a BRCA mutation. Compared with tested women, BRCA nontested women were significantly older (39.1 vs. 49.2 years, P < 0.001), had significantly more preoperative biopsies and mammograms and had fewer previous or simultaneous cancer risk-reducing surgery (oophorectomy). Among BRCA nontested women, common indications for BPM were family history of breast cancer (n = 21, 45.6%) or LCIS or AH (n = 16, 34.8%); 9 nontested women (19.6%) chose BPM based on exclusively on cancer-risk anxiety or personal preference. Most women who underwent BPM did not receive preoperative genetic testing. Further studies are needed to corroborate our findings in other geographic regions and practice settings.

Papillary endothelial hyperplasia in angiokeratoma.

PubMed

Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

2003-01-01

Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia

PubMed Central

Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

2007-01-01

Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. These observations indicate that in some settings, intimal hyperplasia may be part of the disease process of atherosclerosis, and that its formation may be influenced by traditional risk factors for atherosclerosis. PMID:18005873

Thymic cystic degeneration, pseudoepitheliomatous hyperplasia, and hemorrhage in a dog with brodifacoum toxicosis.

PubMed

Rickman, B H; Gurfield, N

2009-05-01

Thymic cysts with pseudoepitheliomatous hyperplasia are described in a 7-month-old female American Eskimo Dog that died of complications from brodifacoum poisoning. Grossly, there was hemothorax with marked cranial mediastinal hemorrhage. Histologically, thymic lobules were expanded and distorted by irregular cysts, lined by single to multiple layers of plump to slightly attenuated polygonal squamous epithelial cells supported by a basement membrane (pseudoepitheliomatous hyperplasia). The thymus had a paucity of lymphocytes and lacked corticomedullary differentiation. Extensive hemorrhage within the cysts and thymic parenchyma extended into the adjacent adipose tissue. To the authors' knowledge, this is the first report of cystic thymic degeneration with pseudoepitheliomatous hyperplasia in a nonhuman species.

Dermatitis, branchitis and mortality in empire gudgeon Hypseleotris compressa exposed naturally to runoff from acid sulfate soils.

PubMed

Callinan, R B; Sammut, J; Fraser, G C

2005-02-28

Severe dermatitis and branchitis are described in a wild population of empire gudgeon Hypseleotris compressa, an Australian eleotrid, exposed naturally to runoff from acid sulfate soils (ASS) in a drained estuarine embayment in eastern Australia. After at least 2 d exposure to pH < 4, and up to 7 d exposure to pH < 6, approximately 50% of the fish sampled had moderate to severe diffuse epidermal hyperplasia, usually at scale margins, and scattered areas of moderate to severe, focal to locally extensive, subacute, necrotising dermatitis. Saprolegnia spp. had invaded epidermis in some inflamed areas. In gills, there was moderate to severe hyperplasia and necrosis of secondary lamellar epithelium, with fusion of adjacent secondary lamellae. Inorganic monomeric aluminium and calcium concentrations in water at the site during the event were 27.7 and 16.6 mg l(-1), respectively. Large numbers of empire gudgeons at the study site had died after at least 8 d exposure to pH < 4, and up to 13 d exposure to pH < 6. These findings provide clear evidence that acidification of estuarine systems by runoff from ASS has deleterious effects on aquatic biota. Furthermore, study findings suggest a mechanism whereby lesions of epizootic ulcerative syndrome (EUS) may be initiated in estuarine fishes by a combination of sublethal exposure to ASS runoff and Aphanomyces invadans infection, a suggestion consistent with the geographic and temporal distribution of EUS outbreaks in Australian estuaries.

Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

PubMed Central

Pfeifer, A M; Lechner, J F; Masui, T; Reddel, R R; Mark, G E; Harris, C C

1989-01-01

The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells. PMID:2538323

Benign prostatic hyperplasia (BPH) management in the primary care setting.

PubMed

Kapoor, Anil

2012-10-01

Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH.

Lymphoid papillary hyperplasia of the palatine tonsil: a Chinese case report

PubMed Central

Zhao, Ming; Yu, Jingjing; Li, Changshui

2013-01-01

Lymphoid papillary hyperplasia is a rare abnormality of the tonsils with a predilection for affecting young Asian girls. Herein, we report a 31-year-old Chinese woman presented as right lateral recurrent tonsillar hypertrophy with odynophagia and dysphagia over the past 5 years, worsening over a period of for half a year. Clinically, this lesion was similar to papillomatosis or lymphoid polyposis. However, histopathologic study showed a distinctive form of lymphoid hyperplasia with considerable distinct finger-like projections composed of many phyllodes which contained remarkable follicular lymphoid hyperplasia. This is the only Chinese case of lymphoid papillary hyperplasia of the palatine tonsils that has been reported in the most recent English literature so far. The importance of recognizing this disorder rests in the fact that in spite of the clinical features suggestive of both a benign and a malignant tumor, however, the process is a benign tumor-like proliferation, probably non-neoplastic, could easily be cured by tonsillectomy. PMID:24040465

Pseudocarcinomatous hyperplasia of the fallopian tube mimicking tubal cancer: a radiological and pathological diagnostic challenge.

PubMed

Lee, Nam Kyung; Choi, Kyung Un; Han, Ga Jin; Kwon, Byung Su; Song, Yong Jung; Suh, Dong Soo; Kim, Ki Hyung

2016-11-14

Pseudocarcinomatous hyperplasia of the fallopian tube is a rare, benign disease characterized by florid epithelial hyperplasia. The authors present the history and details of a 22-year-old woman with bilateral pelvic masses and a highly elevated serum CA-125 level (1,056 U/ml). Ultrasonography and magnetic resonance imaging (MRI) of the pelvis showed bilateral adnexal complex cystic masses with a fusiform or sausage-like shape. Contrast-enhanced fat-suppressed T1-weighted images showed enhancement of papillary projections of the right adnexal mass and enhancement of an irregular thick wall on the left adnexal mass, suggestive of tubal cancer. Based on MRI and laboratory findings, laparotomy was performed under a putative preoperative diagnosis of tubal cancer. The final pathologic diagnosis was pseudocarcinomatous hyperplasia of tubal epithelium associated with acute and chronic salpingitis in both tubes. The authors report a rare case of pseudocarcinomatous hyperplasia of the fallopian tubes mimicking tubal cancer.

High prevalence of atypical hyperplasia in the endometrium of patients with epithelial ovarian cancer.

PubMed

Mingels, Marjanka J J M; Masadah, Rina; Geels, Yvette P; Otte-Höller, Irene; de Kievit, Ineke M; van der Laak, Jeroen A W M; van Ham, Maaike A P C; Bulten, Johan; Massuger, Leon F A G

2014-08-01

The aim of the present study is to determine the prevalence of endometrial premalignancies in women diagnosed with epithelial ovarian cancer (EOC). Endometrial and ovarian specimens of 186 patients with EOC were retrospectively selected using the nationwide pathology network and registry, and sections were comprehensively reviewed: 136 (73%) serous, 19 (10%) endometrioid, 15 (8%) mucinous, seven (4%) clear cell, and nine (5%) undifferentiated. Immunohistochemical phenotypes were compared for patients with serous EOC with concurrent endometrial pathology. In 31%, endometrial (pre)malignancy was found: carcinoma in 3%, endometrial intraepithelial carcinoma (EIC) in 4%, and atypical hyperplasia in 24%. Atypical hyperplasia was found in 47% of endometrioid EOCs but in 7% to 33% of other subtypes. Body mass index was higher concurrent to atypical hyperplasia (P=.001). Serous EOC and EIC immunophenotypes were comparable, whereas atypical hyperplasia was expressed differently. Apart from synchronous endometrial carcinoma, endometrial premalignancies should be taken into account when determining optimal treatment for women diagnosed with EOC. Copyright© by the American Society for Clinical Pathology.

Immunohistochemical differentiation of atypical hyperplasia vs. carcinoma in situ of the breast.

PubMed

Masood, S; Sim, S J; Lu, L

1992-01-01

The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.).

PubMed

Georgiou, Stella; Alami-Durante, Hélène; Power, Deborah M; Sarropoulou, Elena; Mamuris, Zissis; Moutou, Katerina A

2016-02-01

Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth.

Improved Patency of Transjugular Intrahepatic Portosystemic Shunt: The Efficacy of Cilostazol for the Prevention of Pseudointimal Hyperplasia in Swine TIPS Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Sang Woo; Cha, In Ho; Kim, Chul Hwan

Purpose. To investigate the efficacy of oral administration of cilostazol to inhibit pseudointimal/intimal hyperplasia in swine TIPS models. Methods. Successful TIPS creation was carried out in 11 of 12 healthy young pigs (20-25 kg). In the treatment group (n = 6), both cilostazol and aspirin were administered daily, from the first day of TIPS creation. The control group (n = 5) was administered only aspirin. The animals were followed-up for 2 weeks and then killed. The specimen (including portal vein, hepatic parenchymal tract, hepatic vein, and inferior vena cava) and stents were carefully bisected in a longitudinal fashion. The controlmore » group was compared with the treatment group by means of a gross and histologic evaluation of the degree of pseudointimal/intimal hyperplasia in the shunt. Results. At the gross evaluation, the control group showed considerably more pseudointimal/intimal hyperplasia than the treatment group. Using microscopic evaluation, there was a statistically significant difference (p < 0.05) in the mean maximum pseudointimal/intimal hyperplasia thickness between the control group (2.97 {+-} 0.33 mm) and treatment group (0.73 {+-} 0.27 mm). Conclusion. Oral administration of cilostazol may have been effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models.« less

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

DTIC Science & Technology

2006-02-01

will comprise the retrospective study. 15. SUBJECT TERMS Ductal carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability...DCIS who eventually progress to invasive breast cancer is small (4-6). A Danish autopsy study found that 25% of women had in situ carcinomas, including...DCIS, at their death, although the lifetime risk of developing breast cancer during the same period was only 1% (7). Similarly, only 32% of women

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

DTIC Science & Technology

2007-02-01

DCIS tissues, (ii) TC is associated with tumor stage and (iii) TC in DCIS is associated with breast cancer -free survival. 15. SUBJECT TERMS Ductal...carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...DCIS who eventually progress to invasive breast cancer is small (4-6). A Danish autopsy study found that 25% of women had in situ carcinomas

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in situ of the Breast

DTIC Science & Technology

2009-02-01

breast cancer -free survival. 15. SUBJECT TERMS Ductal carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability 16...in 2003 (2,3). However, the fraction of women with DCIS who eventually progress to invasive breast cancer is small (4-6). A Danish autopsy study...found that 25% of women had in situ carcinomas, including DCIS, at their death, although the lifetime risk of developing breast cancer during the same

[GENOMIC VARIABILITY IN PATIENTS WITH DUCTAL FORM OF BREAST CANCER AND THE POSSIBILITY OF CORRECTION THE PEPTIDE BIOREGULATOR AND METAL IONS].

PubMed

Jokhadze, T; Monaselidze, J; Nemsadze, G; Buadze, T; Gaiozishvili, M; Lezhava, T

2017-01-01

Level of genome stability (structural aberrations, aneuploidy and fragile sites) was studied in cells of the lymphocyte culture of ductal breast cancer patients (DBC). Was studied the correctional influence of separate and combinative action of peptide bioregulator (Ala-Glu-Asp-Gly) and heavy metal - nickel. It is shown that DBC patients are characterized by high level of genome instability, which is the result of the chromatin changing state. The used tests makes it possible to conclude that in the case of this form of cancer subordinates to specific epigenetic variation as a hetero- also euchromatic regions of genome. The agents - peptide bioregulator (Ala-Glu-Asp-Gly) and nickel ions, used in cell culture of ductal breast cancer patients, revealed the protective effect what indicates the prospects to further study for their involving purpose in combined therapy of this form of cancer.

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma

PubMed Central

Champanhac, Carole; Teng, I-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong

2015-01-01

Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection. PMID:26603187

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma

NASA Astrophysics Data System (ADS)

Champanhac, Carole; Teng, I.-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong

2015-11-01

Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection.

Evaluation of a levonorgestrel-releasing intrauterine system for treating endometrial hyperplasia in patients with polycystic ovary syndrome.

PubMed

Lin, Min; Xu, XiaoWen; Wang, Yi; Hu, Yue; Zhao, Yu

2014-01-01

To evaluate the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) for treating endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). LNG-IUSs were inserted in 60 PCOS patients with simple (40 cases), irregular (12 cases), or complex (8 cases) endometrial hyperplasia. Follow-ups were performed at 3, 6, 12, and 24 months after insertion. At each time point, changes in menstruation, hemoglobin level, and endometrial thickness and pathology were recorded. Menstrual changes were assessed with the Pictorial Blood Assessment Chart. Hemoglobin levels were measured by the Blood Routine Test. Endometrial thickness was determined by transvaginal ultrasound. Endometrial pathology was defined as simple, irregular, or complex endometrial hyperplasia by a pathologist after curettage. Outcomes at each time point were compared to baseline (pre-insertion) measurements by Student's t test or ANOVA (for multiple comparisons) with the post hoc Dunnett's test. Differences with a p < 0.05 were considered statistically significant. At all time points after LNG-IUS insertion and in all patients, menstrual blood loss was decreased and hemoglobin level was increased significantly compared to pre-insertion levels. The endometrial thickness was significantly reduced in all groups after 12 months. Most patients showed transformation of the endometrial pathology, with complete disappearance of simple and irregular cases of endometrial hyperplasia and a decreased number of complex endometrial hyperplasia cases. LNG-IUS is an effective, safe, nonsurgical, and atraumatic approach with few side effects for the treatment of endometrial hyperplasia in patients with PCOS. © 2014 S. Karger AG, Basel.

Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

PubMed

Al-Jarrah, Muhammed; Matalka, Ismail; Aseri, Hasan Al; Mohtaseb, Alia; Smirnova, Irina V; Novikova, Lesya; Stehno-Bittel, Lisa; Alkhateeb, Ahed

2010-10-11

Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes. FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy. Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats. Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise. Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

[Aromatase activities of endometrial carcinomas and both basic and clinical analyses of endometrial hyperplasia as a premalignant disease].

PubMed

Sasaki, H

1993-08-01

Paraffin-embedded materials obtained from 117 cases of endometrial hyperplasia and 84 cases of carcinoma were used for measurement of both ki-ras and p53 gene mutation and aromatase (ARO) and TGF-alpha immunostaining. The overall incidence of ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%). None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in 3 (13.3%) endometrial carcinomas. The intensity of both ARO and TGF-alpha immunostaining was increased in glands of both hyperplasia and carcinoma, and also in the interstitium of carcinoma. The positive sites of both ARO and TGF-alpha were almost the same, with an incidence below 40% in both hyperplasias and carcinomas. The cultured cells of endometrial carcinoma showed aromatase activity below MCF-7 cells, because testosterone was converted to estradiol (E2). TGF-alpha induced cell growth with at an optimal concentration. In HEC-59 cells, TGF-alpha increased both ARO-activity and mRNA. Some promoters on ARO-exon 1 in HEC-59 cells were different from those in BeWo cells. Progesterone inhibited the E2-induced excretion of pre TGF-alpha in endometrial carcinoma cells. These findings suggest that endometrial hyperplasia can be a premalignant condition of carcinoma, and can be initiated by both ki-ras codon 12 mutation and abnormal activity of ARO induced by TGF-alpha. In addition, HEC-59 cells may possess autocrine/paracrine properties involving ARO, E2 and TGF-alpha.

Genetics Home Reference: 21-hydroxylase deficiency

MedlinePlus

... Urinary Tract Defects Orphanet: Congenital adrenal hyperplasia Screening, Technology, and Research in Genetics (PDF) Vanderbilt Childrens Hospital: Congenital Adrenal Hyperplasia (PDF) Virginia Department of ...

[Surgical treatment of precancer and cancer of endometrium].

PubMed

Ivanov, S; Khadzhiolov, N; Batashki, I

2007-01-01

Our aim was to evaluate occult presence of endometrial cancer in patients with atypical glandular hiperplasia and to compare the histological prognostic factors according to the status of the lymph nodes and the grading of the occult tumour. 306 patients were evaluated retrospectvely for the period of 1990-2007. They were operated one month after the hostological diagnostic atypical glandular hiperplasia obtained by D&C. All patients were with vaginal bleeding. The patients who had concomitant presence of endometrial hyperplasia and endometrial cancer were excluded from the study. One hundred patients (group A) with atypical glandular hyperplasia were compared with 206 patients (group B) without atypical glandular hyperplasia obtained by D&C. Mann and Witney test and chi-square test were used for statistical evaluation.. There was no difference between the age and the menopausal status in the two groups, only there was higher parity in group B. In group A patients with atypical glandular hyperlasia we found in 50% endometrial cancer intraoperatively, in 40% endometrial hyperplasia and in 10% normal endometrium. In the second group B were included the patients without atypical hyperplasia from D&C. In group B were found in 6% endometrial cancer in 44% endometrial hyperplasia and in 50% normal endometrium. In 30 patients was performed complete surgical staging. Six patients were with metastatic lymph nodes. All of them were with grading 2 (4 patients) and grading 3 (2 patients), and also with infiltration in the lymph-vascular spaces. Four patients were with nonendometrioid tumours (type 2 endometrial cancer). The careful preoperative and intraoperative evaluation of the endometrium is very important in patients with atypical glandular hyperplasia. It is reasonable to use frozen section in the time of hysterectomy for patients with atypical glandular hyperplasia. If tumour with grading 2/3 nonendometrioid cancer with lymph-vascular space invasion, is found-complete surgical staging is needed.

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

PubMed

Madas, Balázs G

2016-09-01

There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions

PubMed Central

Kleinberg, David L.; Wood, Teresa L.; Furth, Priscilla A.; Lee, Adrian V.

2009-01-01

Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer chemoprevention by preventing actions of both estrogen and progesterone, especially in women at extremely high risk for developing breast cancer such as BRCA gene 1 or 2 mutations. PMID:19075184

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

PubMed

Singhi, Aatur D; Norwood, Stephanie; Liu, Ta-Chiang; Sharma, Rajni; Wolfgang, Christopher L; Schulick, Richard D; Zeh, Herbert J; Hruban, Ralph H

2013-09-01

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts. As the cysts increase in size, they fuse forming larger cysts. Later lesions demonstrate a unilocular cyst lined by predominantly acinar epithelium with scattered ductal cells. The term cystadenoma, with its neoplastic connotation, does not seem to accurately reflect the histologic, immunohistochemical, or molecular features of these lesions. We suggest readopting the term "acinar cystic transformation" until the non-neoplastic versus neoplastic origin of these lesions can be resolved.

Predicting Sensitivity of Breast Tumors to Src-targeted Therapies Through Assessment of Cas/Src/BCAR3 Activity

DTIC Science & Technology

2017-10-01

expression is elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and DCIS... compared to IDC. (2) BCAR3 is significantly upregulated in triple negative breast cancer and normal tissue; (3) BCAR3 expression shows a modest...expression was seen to be elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and

Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

DTIC Science & Technology

2008-02-01

developing breast cancer during the same period was only 1% (7). Similarly, only 32% of women whose DCIS was misdiagnosed as normal, and so did not receive... breast cancer -free survival. 15. SUBJECT TERMS Ductal carcinoma in situ (DCIS), breast cancer , telomeres, prognosis, genomic instability 16...tumors in women 40-49 years of age in 2003 (2,3). However, the fraction of women with DCIS who eventually progress to invasive breast cancer is small

Metastatic Male Ductal Breast Cancer Mimicking Obstructing Primary Colon Cancer

PubMed Central

Koleilat, Issam; Syal, Anil; Hena, Muhammad

2010-01-01

Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer. PMID:23675178

Obesity is Associated with Atypia in Breast Ductal Lavage of Women with Proliferative Breast Disease

PubMed Central

Djuric, Zora; Edwards, Ann; Madan, Shashi; Darga, Linda; Ren, Jianwei; Koletsky, Mathew; Heilbrun, Lance K.

2009-01-01

Background Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. Methods We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. Results There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity) as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index also was significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Conclusions Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk. PMID:19683484

Obesity is associated with atypia in breast ductal lavage of women with proliferative breast disease.

PubMed

Djuric, Zora; Edwards, Ann; Madan, Shashi; Darga, Linda; Ren, Jianwei; Blake, Cassann; Koletsky, Mathew; Heilbrun, Lance K

2009-10-01

Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.

Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

PubMed

Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

2016-09-01

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. © 2016 UICC.

Comparison of self-expandable and balloon-expanding stents for hybrid ductal stenting in hypoplastic left heart complex.

PubMed

Goreczny, Sebastian; Qureshi, Shakeel A; Rosenthal, Eric; Krasemann, Thomas; Nassar, Mohamed S; Anderson, David R; Morgan, Gareth J

2017-07-01

We aimed to compare the procedural and mid-term performance of a specifically designed self-expanding stent with balloon-expandable stents in patients undergoing hybrid palliation for hypoplastic left heart syndrome and its variants. The lack of specifically designed stents has led to off-label use of coronary, biliary, or peripheral stents in the neonatal ductus arteriosus. Recently, a self-expanding stent, specifically designed for use in hypoplastic left heart syndrome, has become available. We carried out a retrospective cohort comparison of 69 neonates who underwent hybrid ductal stenting with balloon-expandable and self-expanding stents from December, 2005 to July, 2014. In total, 43 balloon-expandable stents were implanted in 41 neonates and more recently 47 self-expanding stents in 28 neonates. In the balloon-expandable stents group, stent-related complications occurred in nine patients (22%), compared with one patient in the self-expanding stent group (4%). During follow-up, percutaneous re-intervention related to the ductal stent was performed in five patients (17%) in the balloon-expandable stent group and seven patients (28%) in self-expanding stents group. Hybrid ductal stenting with self-expanding stents produced favourable results when compared with the results obtained with balloon-expandable stents. Immediate additional interventions and follow-up re-interventions were similar in both groups with complications more common in those with balloon-expandable stents.

Myiasis associated with an invasive ductal carcinoma of the left breast: case study

PubMed Central

Rodrigues, Felipe Tavares; Klemig, Larissa Raquel; Cardozo, Marcos Roberto Pereira; Alves, Paulo Cesar; Aguiar, Valéria Magalhães; Lessa, Claudia Soares

2017-01-01

ABSTRACT Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis. PMID:28591263

Development of ipsilateral chest wall spindle cell carcinoma in a patient with invasive ductal breast carcinoma during postoperative adjuvant therapy: A case report.

PubMed

Li, Kaifu; Kang, Hua; Wang, Yajun; Hai, Tao; Wang, Bixiao

2018-05-01

Metaplastic breast carcinoma (MBC) is rare subtype of breast carcinoma and is regarded as ductal carcinoma that undergoes metaplasia into a glandular growth pattern. Spindle cell carcinoma (SPC) is a subtype of MBC with a predominant spindle cell component. The patient was a 52-year-old female with invasive ductal breast carcinoma who underwent a modified radical mastectomy and an axillary node dissection. A new lump was observed underneath the surgical site between the pectoralis major and pectoralis minor muscles 45 days after the patient underwent sequential postoperative chemotherapy and radiotherapy. It was speculated that the new lesion had developed during postoperative adjuvant therapy. And the new lesion was regarded as a recurrence. We performed a wide dissection of the tumor with negative margins. The pathology of the tumor indicated SPC. Then, the patient received chemotherapy and demonstrated a poor response. Local recurrence and pulmonary metastasis developed shortly afterwards, and the patient succumbed to the disease within 5 months. Local recurrence with metaplastic SPC transformed from invasive ductal breast carcinoma during postoperative chemotherapy and radiotherapy is rare. The failure of subsequent chemotherapy and the progression of disease indicate the aggressive nature of SPC and its decreased sensitivity to chemotherapy and radiotherapy. Further studies must be performed to improve the prognosis of these patients.

Autoimmune pancreatitis type-1 associated with intraduct papillary mucinous neoplasm: report of two cases.

PubMed

Vaquero, Eva C; Salcedo, Maria T; Cuatrecasas, Míriam; De León, Hannah; Merino, Xavier; Navarro, Salvador; Ginès, Angels; Abu-Suboh, Monder; Balsells, Joaquim; Fernández-Cruz, Laureano; Molero, Xavier

2014-01-01

Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at genetically-determined high risk of PDAC often harbor IPMN and/or chronic pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic resection of focal IPMN did not show features of AIP. One of the patients carried a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to normal values after IPMN excision. Common risk factors to IPMN and AIP may facilitate its coincidental generation. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer.

PubMed

Søreide, Kjetil; Sund, Malin

2015-01-28

Pancreatic cancer remains one of the deadliest human cancers with little progress made in survival over the past decades, and 5-year survival usually below 5%. Despite this dismal scenario, progresses have been made in understanding of the underlying tumor biology through among other definition of precursor lesions, delineation of molecular pathways, and advances in genome-wide technology. Further, exploring the relationship between epidemiological risk factors involving metabolic features to that of an altered cancer metabolism may provide the foundation for new therapies. Here we explore how nutrients and caloric intake may influence the KRAS-driven ductal carcinogenesis through mediators of metabolic stress, including autophagy in presence of TP53, advanced glycation end products (AGE) and the receptors (RAGE) and ligands (HMGB1), as well as glutamine pathways, among others. Effective understanding the cancer metabolism mechanisms in pancreatic cancer may propose new ways of prevention and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27.

PubMed

Tokumoto, Masanori; Tsuruya, Kazuhiko; Fukuda, Kyoichi; Kanai, Hidetoshi; Kuroki, Shoji; Hirakata, Hideki; Iida, Mitsuo

2003-06-01

Uraemic patients with advanced secondary hyperparathyroidism (2HPT) have nodular hyperplastic glands with a decreased vitamin D receptor (VDR) density. Previous studies have shown that nodular hyperplasia expressed a significantly lower VDR density as compared with diffuse hyperplasia, and the VDR density negatively correlated with both the glandular weight and the marker of cell proliferation. However, the mechanism by which the decreased VDR density leads to parathyroid cell proliferation remains unclear. In the myelomonocytic cell line, active vitamin D(3) is known to activate the transcription of both p21 and p27, cyclin-dependent kinase inhibitors (CDKIs), regulating the transition from the G(1) to the S phase of the cell cycle, in a VDR-dependent manner. Moreover, the overexpression of p21 and p27 inhibits cell proliferation. In order to elucidate the mechanism of parathyroid cell proliferation, the expression of CDKIs, p21 and p27, and the VDR was analysed immunohistochemically, and compared among nodular and diffuse hyperplastic parathyroid glands, and histologically normal parathyroid glands. The VDR expression in nodular hyperplasias was significantly decreased compared with either diffuse hyperplasias or normal parathyroid glands. The expression of both p21 and p27 was also significantly lower in nodular hyperplasias than in diffuse hyperplasias or normal parathyroid glands. Sections of parathyroid glands with a high expression of nuclear VDR highly expressed both p21 and p27. In nodular hyperplasias, the expression of both p21 and p27 correlated either positively with the nuclear VDR expression or inversely with the glandular weight. Therefore, the reduced expression of p21 and p27, being VDR dependent, is a major pathogenic factor for nodular parathyroid gland growth in advanced 2HPT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldridge, Sandy R.; Covey, Joseph; Morris, Joel

NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100 mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule withmore » a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100 mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. - Highlights: • NSC-743380 induced biliary hyperplasia in rats. • Toxicity of NSC-743380 appears to be related to its anticancer activity. • The model provides an opportunity to explore biomarkers of biliary hyperplasia.« less

The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.

PubMed

Colinot, Darrelle L; Garbuz, Tamila; Bosland, Maarten C; Wang, Liang; Rice, Susan E; Sullivan, William J; Arrizabalaga, Gustavo; Jerde, Travis J

2017-07-01

Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia. © 2017 Wiley Periodicals, Inc.

Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

PubMed

Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

2018-04-30

To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme.

PubMed

Chen, Wenqian; Lu, Cathy; Hirota, Christina; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong

2017-01-01

The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

GLUT-1 Expression in Proliferative Endometrium, Endometrial Hyperplasia, Endometrial Adenocarcinoma and the Relationship Between GLUT-1 Expression and Prognostic Parameters in Endometrial Adenocarcinoma.

PubMed

Canpolat, Tuba; Ersöz, Canan; Uğuz, Aysun; Vardar, Mehmet Ali; Altintaş, Aytekin

2016-01-01

Malignant cells show increased glucose uptake in in vitro and in vivo studies. This uptake is mediated by glucose transporter proteins. GLUT-1 is the most common transporter protein, and its expression is reported to be increase in many human cancers. The aim of this study is to determine the GLUT-1 overexpression in benign, hyperplastic, and malignant endometrial tissues, to evaluate the usefulness of GLUT-1 expression in endometrial hyperplasia, and to determine its role in the neoplastic progression to endometrioid type adenocarcinoma. We also aimed to analyze prognostic clinical parameters, predict prognosis, and survival. We examined immunohistochemical expression of GLUT-1 in 91 cases of endometrial hyperplasia, 100 cases of endometrioid type adenocarcinoma, and 10 proliferative endometrial tissues. The percentage of positive cells and staining intensity were assessed in a semi quantitative fashion and scored (1+ to 3+). GLUT-1 immunoreactivity was not present in proliferative endometrium. Twenty-nine (31.9%) of 91 endometrial hyperplasia cases showed positive immunoreactivity, of which only six were cases of hyperplasia without atypia while 23 of them were cases with atypia. We found GLUT-1 positivity of 95% in endometrioid type adenocarcinoma. GLUT-1 overexpression was not significantly correlated with any of the clinicopathological parameters except histological grade in endometrioid adenocarcinoma; the survival was not found to be correlated with GLUT-1 expression. GLUT-1 immunostaining may be useful in distinguishing hyperplasia without atypia from hyperplasia with atypia; GLUT-1 overexpression is a consistent feature of endometrioid adenocarcinoma. A correlation between GLUT -1 expression and tumor grade has been found, although other prognostic parameters and survival has no meaningful correlation.

Pharmacotherapy for benign prostatic hyperplasia.

PubMed Central

Narayan, P; Indudhara, R

1994-01-01

Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive. Images PMID:7528957

Study of endometrial tissue in dysfunctional uterine bleeding.

PubMed

Kayastha, S

2013-03-01

Dysfunctional uterine bleeding (DUB) is defined as heavy and or irregular menstruation in the absence of recognizable pelvic pathology, pregnancy or general bleeding disorder. Hyperplastic endometrium is abnormal histology finding found in DUB. Out of three type of hyperplasia, atypical type is associated with co-existent ca endometrium and the chance of progression to ca endometrium is very high. Thus this study was conducted to see the incidence of hyperplasia of endometrium in cases of DUB and to see the risk factors for endometrial hyperplasia. It was a prospective study carried out in span of two years (2010 JULY- 2013 Jan) in Nepal Medical College and Teaching Hospital. Hundred cases DUB who under went D&C or hysterectomy were included to study the age range, the relation of parity, patient symptom, contraceptive method and medical disease with the type of endometrial histology. It was found that DUB was common in perimenopusal age (49%) and the incidence increase with the increase of parity. Abnormal endometrial finding (hyperplasia) was found in 31% of the cases. Atypical and complex hyperplasia were associated with irregular menstruation and one third of the hyperplastic patient had hypertension (32.26%). Thus perimenopausal age, irregular menstruation and hypertension are risk factors for hyperplasia. So it is mandatory to do endometrial sampling in cases of perimenopausal age with irregular menstruation withor without hypertension.

Study of denture-induced fibrous hyperplasia cases diagnosed from 1979 to 2001.

PubMed

Macedo Firoozmand, Leily; Dias Almeida, Janete; Guimarães Cabral, Luiz Antonio

2005-01-01

The purpose of this research was to study the cases of inflammatory fibrous hyperplasia (IFH) at the Clinic of Semiology, Department of Bioscience and Oral Diagnosis, São Jose dos Campos Dental School, State University of São Paulo, Brazil. A total of 141 clinical file cards indicating a final diagnosis of IFH, from the archives of the Department of Bioscience and Oral Diagnosis and dated from 1979 to 2001, were included in the study. Of these files, 50 indicated a diagnosis of denture-induced fibrous hyperplasia. Sex, age, race, duration, and clinical features that confirm their classification in the non-neoplastic proliferating process were analyzed statistically. Of the 50 analyzed cases of denture-induced lesion, 22% occurred in men and 78% in women. Patients in the age group of 41 to 50 years presented the highest frequency of the lesion. Inflammatory fibrous hyperplasia occurs more frequently in women (71.63%), and denture-induced lesions appear mainly in patients over 40 years of age (70% of cases). Patients with denture-induced hyperplasia reported pain associated with the lesion (70%).

Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature.

PubMed

Price, Alexandra; Miller, Jason H; Junkins-Hopkins, Jacqueline M

2015-11-01

Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program.

PubMed

Coldman, Andrew; Phillips, Norm

2013-07-09

There has been growing interest in the overdiagnosis of breast cancer as a result of mammography screening. We report incidence rates in British Columbia before and after the initiation of population screening and provide estimates of overdiagnosis. We obtained the numbers of breast cancer diagnoses from the BC Cancer Registry and screening histories from the Screening Mammography Program of BC for women aged 30-89 years between 1970 and 2009. We calculated age-specific rates of invasive breast cancer and ductal carcinoma in situ. We compared these rates by age, calendar period and screening participation. We obtained 2 estimates of overdiagnosis from cumulative cancer rates among women between the ages of 40 and 89 years: the first estimate compared participants with nonparticipants; the second estimate compared observed and predicted population rates. We calculated participation-based estimates of overdiagnosis to be 5.4% for invasive disease alone and 17.3% when ductal carcinoma in situ was included. The corresponding population-based estimates were -0.7% and 6.7%. Participants had higher rates of invasive cancer and ductal carcinoma in situ than nonparticipants but lower rates after screening stopped. Population incidence rates for invasive cancer increased after 1980; by 2009, they had returned to levels similar to those of the 1970s among women under 60 years of age but remained elevated among women 60-79 years old. Rates of ductal carcinoma in situ increased in all age groups. The extent of overdiagnosis of invasive cancer in our study population was modest and primarily occurred among women over the age of 60 years. However, overdiagnosis of ductal carcinoma in situ was elevated for all age groups. The estimation of overdiagnosis from observational data is complex and subject to many influences. The use of mammography screening in older women has an increased risk of overdiagnosis, which should be considered in screening decisions.

US women's attitudes to false positive mammography results and detection of ductal carcinoma in situ: cross sectional survey

PubMed Central

Schwartz, Lisa M; Woloshin, Steven; Sox, Harold C; Fischhoff, Baruch; Welch, H Gilbert

2000-01-01

Objective To determine women's attitudes to and knowledge of both false positive mammography results and the detection of ductal carcinoma in situ after screening mammography. Design Cross sectional survey. Setting United States. Participants 479 women aged 18-97 years who did not report a history of breast cancer. Main outcome measures Attitudes to and knowledge of false positive results and the detection of ductal carcinoma in situ after screening mammography. Results Women were aware that false positive results do occur. Their median estimate of the false positive rate for 10 years of annual screening was 20% (25th percentile estimate, 10%; 75th percentile estimate, 45%). The women were highly tolerant of false positives: 63% thought that 500 or more false positives per life saved was reasonable and 37% would tolerate 10 000 or more. Women who had had a false positive result (n=76) expressed the same high tolerance: 39% would tolerate 10 000 or more false positives. 62% of women did not want to take false positive results into account when deciding about screening. Only 8% of women thought that mammography could harm a woman without breast cancer, and 94% doubted the possibility of non-progressive breast cancers. Few had heard about ductal carcinoma in situ, a cancer that may not progress, but when informed, 60% of women wanted to take into account the possibility of it being detected when deciding about screening. Conclusions Women are aware of false positives and seem to view them as an acceptable consequence of screening mammography. In contrast, most women are unaware that screening can detect cancers that may never progress but feel that such information would be relevant. Education should perhaps focus less on false positives and more on the less familiar outcome of detection of ductal carcinoma in situ. PMID:10856064

Single-cell heterogeneity in ductal carcinoma in situ of breast.

PubMed

Gerdes, Michael J; Gökmen-Polar, Yesim; Sui, Yunxia; Pang, Alberto Santamaria; LaPlante, Nicole; Harris, Adrian L; Tan, Puay-Hoon; Ginty, Fiona; Badve, Sunil S

2018-03-01

Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma in situ was analyzed in a single 5 μm tissue section using a multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, and Na+K+ATPase for cell segmentation). Expression was quantified at cell level using a single-cell segmentation algorithm. K-means clustering was used to determine co-expression patterns of epithelial cell markers and immune markers. We document for the first time the presence of epithelial cell heterogeneity within ducts, between ducts and between patients with ductal carcinoma in situ. There was moderate heterogeneity in a distribution of eight clusters within each duct (average Shannon index 0.76; range 0-1.61). Furthermore, within each patient, the average Shannon index across all ducts ranged from 0.33 to 1.02 (s.d. 0.09-0.38). As the distribution of clusters within ducts was uneven, the analysis of eight ducts might be sufficient to represent all the clusters ie within- and between-duct heterogeneity. The pattern of epithelial cell clustering was associated with the presence and type of immune infiltrates, indicating a complex interaction between the epithelial tumor and immune system for each patient. This analysis also provides the first evidence that simultaneous analysis of both the epithelial and immune/stromal components might be necessary to understand the complex milieu in ductal carcinoma in situ lesions.

Approach to hemorrhoids.

PubMed

Lohsiriwat, Varut

2013-07-01

Hemorrhoids are a very common anorectal disorder defined as the symptomatic enlargement and abnormally downward displacement of anal cushions. The current pathophysiologies of hemorrhoids include the degenerative change of supportive tissue within the anal cushions, vascular hyperplasia, and hyperperfusion of hemorrhoidal plexus. Low-grade hemorrhoids are easily and effectively treated with dietary and lifestyle modification, medical intervention, and some office-based procedures. An operation is usually indicated in symptomatic high-grade and/or complicated hemorrhoids. Whilst hemorrhoidectomy has been the mainstay of surgical treatment, more recently other approaches have been employed including Ligasure hemorrhoidectomy, stapled hemorrhoidopexy, and doppler-guided hemorrhoidal artery ligation. Post-procedural pain and disease recurrence remain the most challenging problems in the treatment of hemorrhoids. This article deals with modern approaches to hemorrhoids based on the latest evidence and reviews of the literature. The management of hemorrhoids in complicated situations is also discussed.

A Case of Masson's Tumor of the Penis Presenting as Chronic Pelvic Pain Syndrome.

PubMed

Yanev, Krasimir; Krastanov, Aleksander; Georgiev, Marincho; Tonev, Andrian; Timev, Alexander; Elenkov, Angel

2018-03-17

The intravascular papillary endothelial hyperplasia (IPEH) or Masson's tumor is an unusual and rare benign disease.It is histologically characterized by papillary and anastomosing channel-like structures lined by proliferating e n dothelium. Radiologically, it is usually presented as a heterogenic solid mass with contrast enhancement, withareas resembling necrosis and thrombosis. These signs can easily be attributed to malignancy. The urogenital tractis extremely rarely affected with only 8 cases described in the kidneys and one of the penis. We present a rarecase of IPEH at the base of the penis, visible only on MRI, causing chronic pelvic pain and erectile dysfunction.According to available English literature our case is the first in this pelvic location and only the second to affect thepenis. Radical excision of the formation cured the condition.

AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

PubMed

Fonseca, L M; do Carmo, M A

2000-01-01

Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

PubMed Central

2013-01-01

Summary Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development. PMID:23990166

A 3D Bioprinted Model for the Study of Premalignant Breast Disease

DTIC Science & Technology

2017-05-01

these glands and performed proof-of-principle 3D printing . We have printed simple ductal structures (tubes) and seeded breast epithelial cells. The...performed proof-of-principle 3D printing . We have printed simple ductal structures (tubes) and seeded breast epithelial cells. The next year we will...All of the PN17 reconstruction data from the 5 completed strains has also been sent to the University of Pittsburg for 3D printing . A summary of the

Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

PubMed Central

Sood, Vikrant; Khanna, Rajeev; Alam, Seema; Rawat, Dinesh; Bhatnagar, Shorav; Rastogi, Archana

2014-01-01

An eleven-year-old clinically dysmorphic and developmentally retarded male child presenting with complaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic portocaval shunt (Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were confirmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed. PMID:24868329

Ductal Carcinoma In Situ: The Whole Truth.

PubMed

Parikh, Ujas; Chhor, Chloe M; Mercado, Cecilia L

2018-02-01

Ductal carcinoma in situ (DCIS) is a noninvasive malignant breast disease traditionally described as a precursor lesion to invasive breast cancer. With screening mammography, DCIS now accounts for approximately 20% of newly diagnosed cancer cases. DCIS is not well understood because of its heterogeneous nature. Studies have aimed to assess prognostic factors to characterize its risk of invasive potential; however, there still remains a lack of uniformity in workup and treatment. We summarize current knowledge of DCIS and the ongoing controversies.

Application of in situ ductal perfusion to facilitate isolation of high-quality RNA from mouse pancreas.

PubMed

Mullin, Anne E; Soukatcheva, Galina; Verchere, C Bruce; Chantler, Janet K

2006-05-01

A technique to isolate high-quality intact RNA from murine pancreas is described. This technique involves in situ ductal perfusion of the pancreas with an RNase inhibitor prior to removal of the organ for RNA extraction. In this way, the pancreatic RNases are inhibited in situ allowing good yields of intact RNA, suitable for studies on pancreatic gene transcription by real-time PCR or microarray analysis, to be obtained in a reliable way.

Congenital adrenal hyperplasia

MedlinePlus

... body produces more androgen, a type of male sex hormone. This causes male characteristics to appear early (or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to ...

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

DTIC Science & Technology

2010-09-01

and interstitial fibrosis, and fibrous pleural adhesions. Other lesions included lymphoid hyperplasia and plasmacytosis, and chronic periadnexal and...inflammation in the lung and mediastinal lymph nodes, chronic inflammation centered on bronchi and vessels, type II pneumocyte hyperplasia , pleural...2/6 33 1/6 16 1/3 33 spleen splenitis, necrotizing 1/3 33 2/6 33 4/6 66 2/3 66 lymphoid depletion 2/3 66 3/6 50 3/6 50 2/3 66 lymphoid hyperplasia * 0

Giant prostatic hyperplasia: report of a previously asymptomatic man presenting with gross hematuria and hypovolemic shock

PubMed Central

Wroclawski, Marcelo Langer; Carneiro, Ariê; Tristão, Rodrigo Alves; Sakuramoto, Paulo Kouiti; Youssef, Jorg Daoud Merched; Lopes, Antonio Correa; Santiago, Lucila Heloísa Simardi; Pompeo, Antonio Carlos Lima

2015-01-01

Giant prostatic hyperplasia is a rare condition characterized by very high volume benign prostatic enlargement (>500g). Few cases have been reported so far and most of them are associated with severe lower urinary symptoms. We report the first case of asymptomatic giant prostatic hyperplasia in an elderly man who had a 720g prostate adenoma, sudden gross hematuria and hypovolemic shock. The patient was successfully treated with open transvesical prostatectomy and had an uneventful postoperative recovery. PMID:26132361

Breast biopsy -- ultrasound

MedlinePlus

... hyperplasia Atypical lobular hyperplasia Flat epithelial atypia Intraductal papilloma Lobular carcinoma-in-situ Radial scar Abnormal results ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.

PubMed

Gu, Xin; Na, Rong; Huang, Tao; Wang, Li; Tao, Sha; Tian, Lu; Chen, Zhuo; Jiao, Yang; Kang, Jian; Zheng, Siqun; Xu, Jianfeng; Sun, Jielin; Qi, Jun

2013-08-01

Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study

PubMed Central

Catanzaro, Daniele; Schäffer, Alejandro A.; Schwartz, Russell

2016-01-01

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with Synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints. PMID:26353381

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

PubMed

Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

2003-02-01

Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

Progress in the study of pancreatic cancer and its pathology.

PubMed

Yanagisawa, A

1998-01-01

Recent advances in diagnostic techniques allow detection of relatively small ductal cancers and mucinous cystic neoplasms of the human pancreas. The histopathological characteristics of a series of such small pancreatic carcinomas encountered in our hospital were: 1) all were invasive ductal carcinomas accompanied by fibrosis, 2) four of seven carcinomas were thought to originate in the branch ducts, 3) no precancerous lesions were found, and 4) lymph node metastasis was detected in only one patient. Mucinous cystic neoplasms were of two types: megacystic and ductectatic. The megacystic type is the classical mucinous cystic neoplasm. The ductectatic type is characterized by the presence of multilocular cysts (reminiscent of bronchiectasia of the lung), and papillary proliferation of the lining epithelium-differing from typical ductal carcinomas as well as from megacystic lesions in terms of morphological features, intrapancreatic location, patient age, and sex. The ductectatic type occurs exclusively in the head and body of the pancreas, and is found predominantly in aging males.

A Single Injection of Interleukin-1 Induces Reversible Aqueous-tear Deficiency, Lacrimal Gland Inflammation, and Acinar and Ductal Cell Proliferation

PubMed Central

Zoukhri, Driss; Macari, Elizabeth; Kublin, Claire L.

2011-01-01

Emerging studies from our laboratory demonstrate that interleukin-1 (IL-1) family members play a major role in impairing lacrimal gland functions. Here we have extended our investigations to observe the effects of IL-1 on aqueous tear production, lacrimal gland secretion, lacrimal gland histology, and acinar and ductal cell proliferation. We demonstrate that a single injection of IL-1 into the lacrimal glands inhibited neurally- as well as agonist-induced protein secretion resulting in decreased tear output. Meanwhile, IL-1 injection induced a severe, but reversible (7–13 days), inflammatory response that led to destruction of lacrimal gland acinar epithelial cells. Finally, we demonstrate that as the inflammatory response subsided and lacrimal gland secretion and tear production returned to normal levels, there was increased proliferation of acinar and ductal epithelial cells. Our work uncovers novel effects of IL-1 on lacrimal gland functions and the potential regenerative capacity of the mouse lacrimal gland. PMID:17362931

Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

PubMed

Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

2016-01-01

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

PubMed

Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

2013-04-05

Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

PubMed Central

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian

2009-01-01

Background The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. Methods and Results we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. Conclusion these data support the activation of neurotensinergic deleterious pathways in breast cancer progression. PMID:19156213

The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

PubMed

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian; Gompel, Anne; Forgez, Patricia

2009-01-01

The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

PubMed

Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

2015-09-01

A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

Benign Prostatic Hyperplasia (BPH)

MedlinePlus

... Benign prostatic hyperplasia (BPH) — also called prostate gland enlargement — is a common condition as men get older. ... There are several effective treatments for prostate gland enlargement, including medications, minimally invasive therapies and surgery. To ...

Oral focal epithelial hyperplasia: report of 3 cases with human papillomavirus DNA sequencing analysis.

PubMed

Gültekin, S E; Tokman Yildirim, Benay; Sarisoy, S

2011-01-01

Focal epithelial hyperplasia (FEH), or Heck's disease, is a benign proliferative viral infection of the oral mucosa that is related to Human Papil-lomavirus (HPV), mainly subtypes 13 and 32. Although this condition is known to exist in numerous populations and ethnic groups, the reported cases among Caucasians are relatively rare. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. Histopathologically, it is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, fusion, and horizontal outgrowth of epithelial ridges and the cells named mitozoids. The purpose of this case report was to present 3 cases of focal epithelial hyperplasia in a pediatric age group. Histopathological and clinical features of cases are discussed and DNA sequencing analysis is reported in which HPV 13, HPV 32, and HPV 11 genomes are detected.

Experimental Evaluation of a New Tubular Coronary Stent (V-Flexª).

PubMed

Shun; Wang; Zhou; Verbeken; Ping; Szilard; Yanming; Jianhua; De Scheerder IK

1998-11-01

The safety, efficacy, angiographic and histological effects of a new 316 L, SS seamless stainless steel tubular stent (V-Flexª, Global Therapeutics, Broomfield, Colorado) was evaluated in a porcine coronary and peripheral artery model. Implantation in the right coronary artery was successful in all 16 pigs. Eight pigs were angiographically controlled after 6 weeks and then sacrificed for morphometric analysis. All stented coronary vessels were widely patent at this moment and morphometric analysis showed only a mild fibromuscular neointimal hyperplasia resulting in a neointimal hyperplasia of 1.15 +/- 0.38 mm2. The remaining 8 pigs were controlled and sacrificed at 12 weeks. At that time, all stented vessels were patent and neointimal hyperplasia was 1.22 +/- 0.34 mm2. Comparison with the Palmaz-Schatzª coronary stent (Cordis, Miami, Florida) in a porcine peripheral artery model demonstrated significantly less neointimal hyperplasia at 6 weeks (1.11 +/- 0.73 vs. 2.40 +/- 0.36, p = 0.001) and at 12 weeks (1.53 +/- 0.42 vs. 2.47 +/- 0.63, p = 0.003) for the V-Flex stent. In conclusion, V-Flex coronary stent implantation in a porcine coronary and peripheral arteries results in a high procedural success rate without subacute thrombotic occlusions, despite no further anticoagulation nor antiplatelet therapy. Six and 12 week histopathological and morphometric evaluation demonstrated only a mild fibromuscular neointimal hyperplasia. Comparison with the Palmaz-Schatz coronary stent in a peripheral artery model showed significantly less neointimal hyperplasia in the V-Flex stent.

Correlation between nasopharyngoscopy and cephalometry in the diagnosis of hyperplasia of the pharyngeal tonsils

PubMed Central

Ritzel, Rodrigo Agne; Berwig, Luana Cristina; da Silva, Ana Maria Toniolo; Corrêa, Eliane Castilhos Rodrigues; Serpa, Eliane Oliveira

2012-01-01

Summary Introduction: Hyperplasia of the pharyngeal tonsil is one of the main causes of mouth breathing, and accurate diagnosis of this alteration is important for proper therapeutic planning. Therefore, studies have been conducted in order to provide information regarding the procedures that can be used for the diagnosis of pharyngeal obstruction. Objective: To verify the correlation between nasopharyngoscopy and cephalometric examinations in the diagnosis of pharyngeal tonsil hyperplasia. Method: This was a cross-sectional, clinical, experimental, and quantitative study. Fifty-five children took part in this study, 30 girls and 25 boys, aged between 7 and 11 years. The children underwent nasofibropharyngoscopic and cephalometric evaluation to determine the grade of nasopharyngeal obstruction. The Spearman's rank correlation coefficient at the 5% significance level was used to verify the correlation between these exams. Results: In the nasopharyngoscopy evaluation, most children showed grade 2 and 3 hyperplasia of the pharyngeal tonsil, which was followed by grade 1. In the cephalometry assessment, most children showed grade 1 hyperplasia of the pharyngeal tonsil, which was followed by grade 2. A statistically significant regular positive correlation was observed between the exams. Conclusion: It was concluded that the evaluation of the pharyngeal tonsil hyperplasia could be carried out by fiber optic nasopharyngoscopy and cephalometry, as these examinations were regularly correlated. However, it was found that cephalometry tended to underestimate the size of the pharyngeal tonsil relative to nasopharyngoscopy. PMID:25991937

[Some morphometric parameters of nucleoli and nuclei in invasive ductal breast carcinomas in women].

PubMed

Karpinska-Kaczmarczyk, Katarzyna

2009-01-01

The purpose of this study was to correlate seven morphometric parameters of nucleoli and nuclei of invasive ductal cancer cells with some clinico-pathological factors such as age, tumor size, axillary lymph node status, MIB-1 proliferation index, and estrogen receptor expression in tumor cells. Methyl green-pyronin Y (MG-PY) was used for simultaneous staining of nuclei and nucleoli in histological sections of 150 invasive ductal breast carcinomas. Next, morphometric parameters of nucleoli and nuclei of tumor cells were measured with computerized image analysis. Nuclear area and number of nucleoli in breast tumor cells were greater in younger axillary node-negative patients. The number of nucleoli and nucleolar shape polymorphism were reduced in tumors measuring 20 mm or less or with lower histological grade. Nuclear area, nucleolar number, and nucleolar polymorphism in carcinomas with low proliferation index and estrogen receptor expression were smaller than in carcinomas with high proliferation index and no estrogen receptor expression. Nucleolar area in primary tumors without axillary node involvement was greater than in tumors with more than three axillary nodes positive. MG-PY selectively and simultaneously stains nucleoli and nuclei of tumor cells enabling standardized and reproducible examination of these structures with computerized image analysis. Univariate statistical analysis disclosed that some morphometric parameters of nucleoli and nuclei of tumor cells correlated with several established clinico-pathological prognostic factors. Therefore, the prognostic significance of these parameters should be studied in a larger group of patients with invasive ductal breast carcinomas.

New experimental method to study acid/base transporters and their regulation in lacrimal gland ductal epithelia.

PubMed

Tóth-Molnár, Edit; Venglovecz, Viktória; Ozsvári, Béla; Rakonczay, Zoltán; Varró, András; Papp, Julius G; Tóth, András; Lonovics, János; Takács, Tamás; Ignáth, Imre; Iványi, Béla; Hegyi, Péter

2007-08-01

The main function of the lacrimal gland is to produce the most aqueous component of the tear film covering the surfaces of the cornea and the conjunctiva. Studies have been conducted that characterize the mixed fluid and protein secretion of isolated acini, but no methods have been developed to characterize lacrimal gland ductal cell (LGDC) secretion. Secretory mechanisms of ductal epithelia may play physiological roles in the maintenance of the standard environments for the cornea and the conjunctiva. In this study, the authors developed a rapid method to isolate large quantities of intact lacrimal ducts. The preparation of isolated intact lacrimal gland ducts for the first time enabled the performance of real-time functional experiments on cleaned ducts. Electron microscopy and fluorescence measurements were used to evaluate the viability of lacrimal ducts. Fluorescence measurements showed that LGDCs express functionally active Na(+)/H(+) exchanger (NHE) and Cl(-)/HCO(3)(-) exchanger (AE). Parasympathomimetic stimulation by carbachol stimulated NHE and AE through the elevation of intracellular calcium concentration. This mechanism can play a role in the regulation of ion and water secretion by LGDCs. The authors have described a lacrimal gland duct isolation technique in which the intact ducts remain viable and the role of duct cells in tear film secretion can be characterized. These data combined with the novel isolation facilitated understanding of the regulation mechanisms of ductal cell secretion at cellular and molecular levels under normal and pathologic conditions.

The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma.

PubMed

Zhu, Yi; Zhang, Jing-jing; Zhu, Rong; Zhu, Yan; Liang, Wen-biao; Gao, Wen-tao; Yu, Jun-bo; Xu, Ze-kuan; Miao, Yi

2011-12-01

The MUC4 gene could have a key role in the progression of pancreatic cancer, but the quantitative measurement of its expression in clinical tissue samples remains a challenge. The correlations between MUC4 promoter methylation status in vivo and either pancreatic cancer progression or MUC4 mRNA expression need to be demonstrated. We used the techniques of quantitative real-time PCR and DNA methylation-specific PCR combined microdissection to precisely detect MUC4 expression and promoter methylation status in 116 microdissected foci from 57 patients with pancreatic ductal adenocarcinoma. Both mRNA expression and hypomethylation frequency increased from normal to precancerous lesions to pancreatic cancer. Multivariate Cox regression analysis showed that high-level MUC4 expression (P = 0.008) and tumor-node-metastasis staging (P = 0.038) were significant independent risk factors for predicting the prognosis of 57 patients. The MUC4 mRNA expression was not significantly correlated with promoter methylation status in 30 foci of pancreatic ductal adenocarcinoma. These results suggest that high mRNA expression and hypomethylation of the MUC4 gene could be involved in carcinogenesis and in the malignant development of pancreatic ductal adenocarcinoma. The MUC4 mRNA expression may become a new prognostic marker for pancreatic cancer. Microdissection-based quantitative real-time PCR and methylation-specific PCR contribute to the quantitative detection of MUC4 expression in clinical samples and reflect the epigenetic regulatory mechanisms of MUC4 in vivo.

Low abundance of sweat duct Cl− channel CFTR in both healthy and cystic fibrosis athletes with exceptionally salty sweat during exercise

PubMed Central

Haack, Karla K. V.; Pollack, Brian P.; Millard-Stafford, Mindy; McCarty, Nael A.

2011-01-01

To understand potential mechanisms explaining interindividual variability observed in human sweat sodium concentration ([Na+]), we investigated the relationship among [Na+] of thermoregulatory sweat, plasma membrane expression of Na+ and Cl− transport proteins in biopsied human eccrine sweat ducts, and basal levels of vasopressin (AVP) and aldosterone. Lower ductal luminal membrane expression of the Cl− channel cystic fibrosis transmembrane conductance regulator (CFTR) was observed in immunofluorescent staining of sweat glands from healthy young adults identified as exceptionally “salty sweaters” (SS) (n = 6, P < 0.05) and from patients with cystic fibrosis (CF) (n = 6, P < 0.005) compared with ducts from healthy young adults with “typical” sweat [Na+] (control, n = 6). Genetic testing of healthy subjects did not reveal any heterozygotes (“carriers”) for any of the 39 most common disease-causing CFTR mutations in the United States. SS had higher baseline plasma [AVP] compared with control (P = 0.029). Immunostaining to investigate a potential relationship between higher plasma [AVP] (and sweat [Na+]) and ductal membrane aquaporin-5 revealed for all groups a relatively sparse and location-dependent ductal expression of the water channel with localization primarily to the secretory coil. Availability of CFTR for NaCl transport across the ductal membrane appears related to the significant physiological variability observed in sweat salt concentration in apparently healthy humans. At present, a heritable link between healthy salty sweaters and the most prevalent disease-causing CFTR mutations cannot be established. PMID:21228336

Bilateral DCIS following gynecomastia surgery. Role of nipple sparing mastectomy. A case report and review of literature☆

PubMed Central

Noor, L.; McGovern, P.; Bhaskar, P.; Lowe, J.W.

2011-01-01

Bilateral ductal carcinoma in situ of breast is a very rare disease in men. Ductal carcinoma in situ (DCIS) is an abnormal proliferation that involves the ductal epithelium and it has the potential of evolving into an invasive tumour. Gynaecomastia (female like breast in men) is a benign condition though it is associated with a reported 3% incidence of unilateral invasive breast cancer.2 Synchronous bilateral breast cancer in association with gynaecomastia is exceptionally rare. The recommended treatment for DCIS in male is mastectomy. So far only 2 cases of bilateral DCIS in male patients has been reported in the literature treated with skin and nipple sparing mastectomies. We report another case of synchronous bilateral DCIS in a male treated with skin and nipple sparing mastectomies. A 44 year-old man with history of long-standing gynecomastia. He had no identifiable risk factor for the development of cancer. His pre operative assessment of breast including mammograms was normal. He underwent bilateral subcutaneous mastectomies, with subsequent incidental diagnosis of synchronous bilateral ductal carcinoma in situ. The case was discussed in multidisciplinary team meeting and the need for further surgery was felt including excision of nipple areola complex. However considering patient wishes, cosmetic outcome and recent literature it was decided to preserve nipple areola complex (NAC) with regular follow up evaluation. Our patient at completion of 18 months of treatment is doing well with no signs of local recurrence. PMID:22096697

Ltbp1L is focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution

PubMed Central

2013-01-01

Introduction Latent TGFβ binding proteins (LTBPs) govern TGFβ presentation and activation and are important for elastogenesis. Although TGFβ is well-known as a tumor suppressor and metastasis promoter, and LTBP1 is elevated in two distinct breast cancer metastasis signatures, LTBPs have not been studied in the normal mammary gland. Methods To address this we have examined Ltbp1 promoter activity throughout mammary development using an Ltbp1L-LacZ reporter as well as expression of both Ltbp1L and 1S mRNA and protein by qRT-PCR, immunofluorescence and flow cytometry. Results Our data show that Ltbp1L is transcribed coincident with lumen formation, providing a rare marker distinguishing ductal from alveolar luminal lineages. Ltbp1L and Ltbp1S are silent during lactation but robustly induced during involution, peaking at the stage when the remodeling process becomes irreversible. Ltbp1L is also induced within the embryonic mammary mesenchyme and maintained within nipple smooth muscle cells and myofibroblasts. Ltbp1 protein exclusively ensheaths ducts and side branches. Conclusions These data show Ltbp1 is transcriptionally regulated in a dynamic manner that is likely to impose significant spatial restriction on TGFβ bioavailability during mammary development. We hypothesize that Ltbp1 functions in a mechanosensory capacity to establish and maintain ductal luminal cell fate, support and detect ductal distension, trigger irreversible involution, and facilitate nipple sphincter function. PMID:24262428

Tumescent power liposuction in the treatment of the enlarged male breast.

PubMed

Boni, Roland

2006-01-01

Tumescent power liposuction is widely used on various parts of the body for minimal-access lipectomy. The undesired fat deposits are injected with tumescence fluid containing saline, epinephrine, bicarbonate and lidocaine; the latter is used as the only source of pain control. The fat is then removed using vibrating microcannulas. To evaluate the value of tumescent power liposuction in the treatment of the enlarged male breast. 38 male patients aged 23-64 years (mean age 39.8 +/- 9.7 years) with enlarged breasts were enrolled in the study. In 32 patients, breasts were enlarged due to fat tissue, and the ductal glands were not palpable (pseudogynecomastia). In 6 patients, the ductal glands were enlarged (gynecomastia). All patients were treated with tumescent liposuction over a 2-year period using a single entry site from the axillary fossa. Both fat as well as ductal and stromal tissue were removed by microcannulas. None of the patients had early postoperative complications of infection, hematoma or seroma. There were no treatment-induced asymmetries, contour deformities or irregularities. No open excision or skin reduction procedures were required. Tumescent liposuction using a single entry site in the axillary fossa is a minimally invasive technique to treat enlarged male breasts. Both fat (pseudogynecomastia in adipose patients) as well as ductal and stromal tissue (in gynecomastia) can be removed with tumescent liposuction, resulting in a high level of patient satisfaction. Copyright 2006 S. Karger AG, Basel.

Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.

PubMed

Grimm, Lars J; Ghate, Sujata V; Hwang, E Shelley; Soo, Mary Scott

2017-11-01

The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS). We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded. In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications. Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer.

PubMed

Kojima, Fumiyoshi; Koike, Hiroyuki; Matsuzaki, Ibu; Iwahashi, Yoshifumi; Warigaya, Kenji; Fujimoto, Masakazu; Ono, Kazuo; Urata, Youji; Kohjimoto, Yasuo; Hara, Isao; Murata, Shin-Ichi

2017-04-01

Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of prostate cancer performed based on gross cystic appearance have been reported. MPA can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed extraprostatic invasion; however, none of the patients experienced recurrence during the follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level and tumor size and location. In conclusion, we demonstrated that MPA is a ductal adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different clinicopathololgical appearances. Copyright © 2017 Elsevier Inc. All rights reserved.

Flat epithelial atypia of the breast: pathological-radiological correlation.

PubMed

Solorzano, Silma; Mesurolle, Benoît; Omeroglu, Attila; El Khoury, Mona; Kao, Ellen; Aldis, Ann; Meterissian, Sarkis

2011-09-01

This study was undertaken to determine the prevalence of flat epithelial atypia at ultrasound-guided and stereotactically guided needle biopsies, to describe the mammographic and sonographic features of flat epithelial atypia, and to determine the significance of lesions diagnosed as flat epithelial atypia at imaging-guided needle biopsies. Retrospective review of a database of 1369 consecutive sonographically and stereotactically guided needle biopsies performed during a 12-month period yielded 33 lesions with flat epithelial atypia as the most severe pathologic entity (32 patients). Two radiologists retrospectively reviewed the imaging presentation, by combined consensus, according to the BI-RADS lexicon. Twenty-two of 33 flat epithelial atypia diagnoses (67%) were obtained under stereotactic guidance, and 11 (33%) were obtained under sonographic guidance. Six patients had synchronous breast cancer. Flat epithelial atypia lesions presented mammographically most often as microcalcifications (20/33 [61%]) distributed in a cluster (14/20 [70%]) with amorphous morphology (13/20 [65%]). Sonographically, flat epithelial atypia lesions appeared most often as masses (9/11 [82%]), with an irregular shape (6/9 [67%]), microlobulated margins (5/9 [56%]), and hypoechoic or complex echotexture (7/9 [78%]). Twenty-eight of 33 lesions (85%) were surgically excised, confirming the flat epithelial atypia diagnosis in 11 of the 28 lesions (39%), yielding carcinoma in four (14%) and atypical ductal hyperplasia in six (21%). Columnar cell changes without atypia were diagnosed in four lesions (14%), and lobular carcinoma in situ was diagnosed in three lesions (11%). Mammographic and sonographic presentation of flat epithelial atypia is not specific (clustered amorphous microcalcifications and irregular, hypoechoic or complex masses). Given the underestimation rate of malignancy, surgical excision should be considered when imaging-guided biopsy yields flat epithelial atypia.

Benign Breast Disease, Mammographic Breast Density, and the Risk of Breast Cancer

PubMed Central

2013-01-01

Background Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk. Methods We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided. Results Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses. Conclusions Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis. PMID:23744877

Hepatobiliary and Pancreatic neoplasms in patients with McCune-Albright syndrome.

PubMed

Gaujoux, Sébastien; Salenave, Sylvie; Ronot, Maxime; Rangheard, Anne-Sophie; Cros, Jérôme; Belghiti, Jacques; Sauvanet, Alain; Ruszniewski, Philippe; Chanson, Philippe

2014-01-01

McCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms. The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome. Nineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012. Six (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation. We describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.

High-Risk Breast Lesions: A Machine Learning Model to Predict Pathologic Upgrade and Reduce Unnecessary Surgical Excision.

PubMed

Bahl, Manisha; Barzilay, Regina; Yedidia, Adam B; Locascio, Nicholas J; Yu, Lili; Lehman, Constance D

2018-03-01

Purpose To develop a machine learning model that allows high-risk breast lesions (HRLs) diagnosed with image-guided needle biopsy that require surgical excision to be distinguished from HRLs that are at low risk for upgrade to cancer at surgery and thus could be surveilled. Materials and Methods Consecutive patients with biopsy-proven HRLs who underwent surgery or at least 2 years of imaging follow-up from June 2006 to April 2015 were identified. A random forest machine learning model was developed to identify HRLs at low risk for upgrade to cancer. Traditional features such as age and HRL histologic results were used in the model, as were text features from the biopsy pathologic report. Results One thousand six HRLs were identified, with a cancer upgrade rate of 11.4% (115 of 1006). A machine learning random forest model was developed with 671 HRLs and tested with an independent set of 335 HRLs. Among the most important traditional features were age and HRL histologic results (eg, atypical ductal hyperplasia). An important text feature from the pathologic reports was "severely atypical." Instead of surgical excision of all HRLs, if those categorized with the model to be at low risk for upgrade were surveilled and the remainder were excised, then 97.4% (37 of 38) of malignancies would have been diagnosed at surgery, and 30.6% (91 of 297) of surgeries of benign lesions could have been avoided. Conclusion This study provides proof of concept that a machine learning model can be applied to predict the risk of upgrade of HRLs to cancer. Use of this model could decrease unnecessary surgery by nearly one-third and could help guide clinical decision making with regard to surveillance versus surgical excision of HRLs. © RSNA, 2017.

Study of nuclear morphometry on cytology specimens of benign and malignant breast lesions: A study of 122 cases

PubMed Central

Kashyap, Anamika; Jain, Manjula; Shukla, Shailaja; Andley, Manoj

2017-01-01

Background: Breast cancer has emerged as a leading site of cancer among women in India. Fine needle aspiration cytology (FNAC) has been routinely applied in assessment of breast lesions. Cytological evaluation in breast lesions is subjective with a “gray zone” of 6.9–20%. Quantitative evaluation of nuclear size, shape, texture, and density parameters by morphometry can be of diagnostic help in breast tumor. Aims: To apply nuclear morphometry on cytological breast aspirates and assess its role in differentiating between benign and malignant breast lesions with derivation of suitable cut-off values between the two groups. Settings and Designs: The present study was a descriptive cross-sectional hospital-based study of nuclear morphometric parameters of benign and malignant cases. Materials and Methods: The study included 50 benign breast disease (BBD), 8 atypical ductal hyperplasia (ADH), and 64 carcinoma cases. Image analysis was performed on Papanicolaou-stained FNAC slides by Nikon Imaging Software (NIS)–Elements Advanced Research software (Version 4.00). Nuclear morphometric parameters analyzed included 5 nuclear size, 2 shape, 4 texture, and 2 density parameters. Results: Nuclear morphometry could differentiate between benign and malignant aspirates with a gradually increasing nuclear size parameters from BBD to ADH to carcinoma. Cut-off values of 31.93 μm2, 6.325 μm, 5.865 μm, 7.855 μm, and 21.55 μm for mean nuclear area, equivalent diameter, minimum feret, maximum ferret, and perimeter, respectively, were derived between benign and malignant cases, which could correctly classify 7 out of 8 ADH cases. Conclusion: Nuclear morphometry is a highly objective tool that could be used to supplement FNAC in differentiating benign from malignant lesions, with an important role in cases with diagnostic dilemma. PMID:28182052

Study of nuclear morphometry on cytology specimens of benign and malignant breast lesions: A study of 122 cases.

PubMed

Kashyap, Anamika; Jain, Manjula; Shukla, Shailaja; Andley, Manoj

2017-01-01

Breast cancer has emerged as a leading site of cancer among women in India. Fine needle aspiration cytology (FNAC) has been routinely applied in assessment of breast lesions. Cytological evaluation in breast lesions is subjective with a "gray zone" of 6.9-20%. Quantitative evaluation of nuclear size, shape, texture, and density parameters by morphometry can be of diagnostic help in breast tumor. To apply nuclear morphometry on cytological breast aspirates and assess its role in differentiating between benign and malignant breast lesions with derivation of suitable cut-off values between the two groups. The present study was a descriptive cross-sectional hospital-based study of nuclear morphometric parameters of benign and malignant cases. The study included 50 benign breast disease (BBD), 8 atypical ductal hyperplasia (ADH), and 64 carcinoma cases. Image analysis was performed on Papanicolaou-stained FNAC slides by Nikon Imaging Software (NIS)-Elements Advanced Research software (Version 4.00). Nuclear morphometric parameters analyzed included 5 nuclear size, 2 shape, 4 texture, and 2 density parameters. Nuclear morphometry could differentiate between benign and malignant aspirates with a gradually increasing nuclear size parameters from BBD to ADH to carcinoma. Cut-off values of 31.93 μm 2 , 6.325 μm, 5.865 μm, 7.855 μm, and 21.55 μm for mean nuclear area, equivalent diameter, minimum feret, maximum ferret, and perimeter, respectively, were derived between benign and malignant cases, which could correctly classify 7 out of 8 ADH cases. Nuclear morphometry is a highly objective tool that could be used to supplement FNAC in differentiating benign from malignant lesions, with an important role in cases with diagnostic dilemma.

Benign breast disease, mammographic breast density, and the risk of breast cancer.

PubMed

Tice, Jeffrey A; O'Meara, Ellen S; Weaver, Donald L; Vachon, Celine; Ballard-Barbash, Rachel; Kerlikowske, Karla

2013-07-17

Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk. We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided. Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses. Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.

Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice.

PubMed

Bidinotto, Lucas T; Costa, Celso A R A; Salvadori, Daisy M F; Costa, Mirtes; Rodrigues, Maria A M; Barbisan, Luís F

2011-08-01

This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi-organ carcinogenesis bioassay induced by 7,12-dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4-hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In the short-term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg⁻¹ (five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg⁻¹ treated group showed significantly lower (P < 0.01) leukocyte DNA damage than its respective positive group exposed to MNU alone at week 3. In the medium-term study, DDB-initiated mice were allocated into three groups: vehicle group (positive control) and LGEO 125 or 500 mg kg⁻¹ (five times per week for 6 weeks; test groups). At week 20, all animals were euthanized and mammary glands, colon and urinary bladder were processed for histopathological analyses for detection of preneoplastic and neoplastic lesions. A slight non-significant effect of treatment with LGEO 500 mg kg⁻¹ in reducing development of alveolar and ductal mammary hyperplasia was found (P = 0.075). Our findings indicate that lemongrass essential oil provided protective action against MNU-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB-initiated female Balb/C mice. Copyright © 2010 John Wiley & Sons, Ltd.